Recombinant human cytomegalovirus vaccine

ABSTRACT

Infection of human fibroblast cells with human cytomegalovirus (HCMV) causes down regulation of cell surface expression of MHC class I. The present invention is directed to a mutant with a 9-kb deletion in the S component of the HCMV genome (including open reading frames IRS1-US9 and US11) which failed to down regulate class I heavy chains. By examining the phenotypes of mutants with smaller deletions with this portion of the HCMV genome, a 7-kb region containing at least 9 open reading frames was shown to contain the genes required for reduction in heavy chain expression. Furthermore, it was determined that two subregions (A and B) of the 7-kb region each contained genes which were sufficient to cause heavy chain down regulation. In subregion B, the US11 gene product is involved. It encodes a endoglycosidase H-sensitive glycoprotein which is intracytoplasmic, similar to the adenovirus type 2 E3-19K glycoprotein which inhibits surface expression of class I heavy chains.

This is a divisional of application Ser. No. 08/282,696 filed on Jul. 29, 1994.

FIELD OF THE INVENTION

The present invention relates to recombinant mutant human cytomegalovirus (HCMV) which does not down regulate expression of cellular MHC class I heavy chains upon infection.

BACKGROUND OF THE INVENTION

Human cytomegalovirus (HCMV) is a betaherpesvirus which causes clinically serious disease in immunocompromised and immunosuppressed adults, as well as in some infants infected in in utero or perinatally (Alford and Britt, 1990). The 230-kb dsDNA genome of HCMV was sequenced (Chee et al., 1990) and has at least 200 open reading frames (ORFs). For purposes of this application, open reading frame is defined as the portion of a gene which encodes a string of amino acids and hence may encode a protein, The function of some HCMV proteins are known or predicted due to their homology with other vital (esp. herpes simplex virus)rand cellular proteins. However, for the majority of the HCMV ORFs, the function(s) of the proteins they encode is unknown.

In order to study HCMV gene function HCMV deletion mutants can be constructed in order to assess their in vitro growth properties (Jones et al., 1991; Jones and Muzithras, 1992). For purposes of this application deletion mutants are defined as human cytomegalovirus mutants which lack regions of the wild-type vital genome. This strategy involves site-directed replacement mutagenesis of selected HCMV gene(s) by a prokaryotic reporter gene, usually β-glucuronidase, although guanosine phosphoribosyltransferase can also be used. In this fashion, the recombinant virus can-be isolated only if the replaced vital gene(s) is nonessential.

Several investigators have shown that infection by HCMV results in the down regulation of cellular MHC class I heavy chains (Browne et al., 1990;Beersma et al., 1993; Yamashita et al., 1993). For purposes of this application, down regulation is defined as reduction in either synthesis, stability or surface expression of MHC class I heavy chains. Such a phenomenon has been reported for some other DNA viruses, including adenovirus, murine cytomegalovirus, and herpes simplex virus (Anderson et al., 1985; Burget and Kvist, 1985; del Val et al., 1989; Campbell et al., 1992; Campbell and Slater, 1994; York et al., 1994). In the adenovirus and herpes simplex virus systems, the product of a viral gene which is dispensable for replication in vitro is sufficient to cause down regulation of MHC class I heavy chains (Anderson et al.., 1985; Burget and Kvist, 1985). The gene(s) involved in class I heavy chain down regulation by murine cytomegalovirus have not yet been identified.

SUMMARY OF THE INVENTION

The present invention is directed to a recombinant mutant human cytomegalovirus which does not down regulate expression of cellular MHC class I heavy chains upon infection. Mutants RV 798 and RV 799 both deleted of open reading frames US2-US11, lose the ability to down regulate MHC class I heavy chains.

The present invention is also directed to a method to produce the recombinant mutant human cytomegalovirus and a vaccine which utilizes the cytomegalovirus. One skilled in the art will use live attenuated HCMV vaccine lacking this gene region in order to elicit a better immune response, than one containing this gene region, based on the lack of class I down registration by the former. Therefore a virus lacking the region is a superior immunogen.

In addition, the HCMV gene involved in the MHC class I heavy chain down regulation can be incorporated into adenovirus vectors or similar virus based gene therapy vectors to minimize the immune response which will allow the use of the recombinant adenovirus or similar virus based gene therapy vectors to be used in gene therapy.

The invention may be more fully understood by reference to the following drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. Detection of cell surface MHC class I by immunofluorescence-flow cytometry in HCMV-infected cells. Human foreskin fibroblast (HFF) cells were infected with the indicated virus at a multiplicity of infection of 5 PFU/cell for 72 h. At that time, cells were fixed in 1% paraformaldehyde and stained with primary antibody specific for HLA-A, B, C (W6/32) or control mouse IgG (isotype matched) followed by secondary FITC-conjugated goat anti-mouse-IgG. Percent positive cells (5×10³ total) and mean fluorescent intensity (MFI) were calculated on the basis of forward angle light scatter versus log-integrated 90° light scatter using the Immuno Program, Coulter MDADS I.

FIGS. 2A-2C Expression of MHC class I heavy chains in HCMV wild-type strain AD169-infected cells. FIG. 2A is a Western blot analysis. HFF cells were uninfected (U) or infected at a multiplicity of infection of 5 PFU/cell. At 24, 48, and 72 h postinfection total cellular proteins were harvested, electrophoresed through a 15% SDS-polyacrylamide gel, electroblotted to nitrocellulose, and probed with TP25.99 murine monoclonal antibody (specific for a non-conformational epitope on MHC class I heavy chains) using an ECL chemiluminescent detection kit (Amersham) FIGS. 2B and C are immunoprecipitation analyses. HFF cells were uninfected or infected (as above), either in the absence or presence (+PFA) of phosphonoformate and radiolabeled either for 4 h at late times postinfection (69-73 h) (FIG. 2B) or for 2 h at the indicated time postinfection (FIG. 2C). Proteins were harvested immediately after radiolabeling and class I heavy chains were immunoprecipitated using TP25.99 murine monoclonal antibody.

FIGS. 3A-3J Organization of recombinant virus genomes. FIG. 3A, the first line is a schematic of the overall organization of the HCMV wild-type genome. Unique region sequences are shown by a line, while repeated region sequences are indicated by shaded boxes. Relevant HindIII fragments, within the L and S components, are indicated by letter designation (Oram et al., 1982). The second line is an expansion of the wild-type HindIII-Q, -X, and -V regions of the S component. The significant open reading frames, and their orientation, are shown as open boxes (Chee et al., 1990). The position of the IRS repeated sequences is indicated by the shaded rectangle, The locations of HindIII (H) and XhoI (X) restriction endonuclease sites are shown. FIGS. 3B-I show the genomic organization of the indicated HCMV mutant. In each case, the first line is the organization of the AD169 wild-type genome, the second line represents the organization of relevant sequences of the linearized plasmid used to make the recombinant virus. The slanted lines indicate the boundaries of the viral flanking sequences which may be involved in homologous recombination to create the desired mutation. The region deleted is indicated by a shaded box below the first line. FIG. 3J shows the derivation and organization of RV799. The first two lines are the same representations as FIGS. 3B-I, and the third line represents the organization of the relevant sequences of the linearized plasmid used to make RV799 from the RV134 parent (second line).

FIGS. 4A-4C show the analysis of heavy chain expression in cells infected With HCMV mutants. HFF cells were uninfected (U) or infected with the indicated virus (multiplicity of infection of 5 PFU/cell) and radiolabeled for 4 h at late times postinfection (69-73 h). Proteins were harvested immediately after radiolabeling. FIG. 4A is a radiograph of class I heavy chains which were immunoprecipitated using TP25.99 murine monoclonal antibody. FIG. 4B is a radiograph of radiolabeled proteins to verify approximately equivalent radiolabeling efficiency. FIG. 4C is a radiograph to verify equal progression through the vital replicative cycle. UL80 proteins were immunoprecipitated using anti-assembly protein rabbit polyclonal antiserum.

FIGS. 5A-5C shows immunoprecipitation of class I heavy chains from RV798-, RV799-, RV134-, or AD169 wild-type-infected cells. HFF cells were uninfected (U) or infected with the indicated virus (multiplicity of infection of 5 PFU/cell) and radiolabeled for 2 h at late times postinfection (71-73 h). Proteins were harvested immediately after radiolabeling. FIG. 5A is a radiograph of class I heavy chains which were immunoprecipitated using TP25.99 murine monoclonal antibody. Equivalent radiolabeling efficiency (FIG. 5B) and progression through the viral replicative cycle (FIG. 5C) were verified as described for FIGS. 4B and 4C.

FIG. 6 is a radiograph showing the endoglycosidase H sensitivity of class I heavy chains synthesized in RV798-infected cells. HFF cells were infected with RV798 (multiplicity of infection of 5 PFU/cell) and radiolabeled for 2 h at early times (6-8 h) or late times (80-82 h) postinfection. For comparison purposes, uninfected cells were radiolabeled for 2 h. Proteins were harvested either immediately after radiolabeling (pulse) or after a 2 h chase (chase) in complete unlabeled media. Class I heavy chains were immunoprecipitated using TP25.99 murine monoclonal antibody. Immunoprecipitated protein were incubated for 6 h either in the presence (+) or absence (-) of 1.5 mU of endoglycosidase H, prior to SDS-polyacrylamide gel electrophoresis and fluorography.

FIGS. 7A-7C show the immunoprecipitation of class I heavy chains from RV798-, RV7181-, RV7177-, or AD169 wild-type-infected cells. HFF cells were uninfected (U) or infected with the indicated virus (multiplicity of infection of 5 PFU/cell) and radiolabeled for 2 h at late times postinfection (65-67 h). Proteins were harvested immediately after radiolabeling. FIG. 7A is a radiograph of class I heavy chain which were immunoprecipitated using TP25.99 murine monoclonal antibody. Equivalent radiolabeling efficiency (FIG. 7B) and progression through the viral replicative cycle (FIG. 7C) were verified as described for FIG. 4B-C.

FIGS. 8A-8D are photographs which show localization of US11 gene product (gpUS11) in infected cells by immunofluorescence, HFF cells were uninfected or infected with either AD169 wild-type or RV699 (deleted of the US11 gene) at a multiplicity of infection of 5 PFU/cell, After 8 h, uninfected and infected cells were fixed with 4% paraformaldehyde. Some cells were then permeabilized with 0.2% "TRITON X-100" (alkylaryl polyether alcohol). The primary antibody was rabbit polyclonal antisera raised against a US11 fusion protein (Jones and Muzithras, 1991), Fluorescence was visualized through a Zeiss microscope.

FIGS. 9A-9D show analysis of heavy chain expression in cells infected with HCMV mutants at early times postinfection, HFF cells were uninfected (U) or infected with the indicated virus (multiplicity of infection of 5 PFU/cell) and radiolabeled for 4 h from 6-10 h postinfection. Proteins were harvested immediately after radiolabeling. FIG. 9A is a radiograph of class I heavy chains were immunoprecipitated using TP25,99 murine monoclonal antibody. FIG. 9B is a radiograph in which, to verify approximately equal infection, the 72-kDa IE1 immediate-early protein was immunoprecipitated using the murine monoclonal antibody 9221. FIG. 9C is a radiograph of the immunoprecipitation of the cellular transferrin receptor with murine monoclonal antibody Bet-T9 to verify approximately equal expression of this glycoprotein.

FIG. 9D is a radiograph of total radiolabeled proteins to verify approximately equivalent radiolabeling efficiency.

FIGS. 10A-10C provide a summary of MHC class I heavy chain expression data from HFF cells infected with wild-type and mutant HCMV. In FIG. 10A, the first line is the overall organization of the HCMV wild-type genome, and the second line is an expansion of the wild-type HindIII-Q and -X regions of the S component. The ORFs are indicated by an unshaded rectangle; the unlabeled ORF overlapping US4 and US5 is US4.5.In FIG. 10(B), the deletions within the various HCMV mutants are indicated by the shaded rectangle. RV670 is deleted of IRS1-US9 and US11; RV35 is deleted of US6-US11; RV67 is deleted of US10-US11; RV80 is deleted of US8-U89; RV725 is deleted of US7; RV69 is deleted of US6; RV47 is deleted of US2-US3; RV5122 is deleted of US1; RV46 is deleted of IRS1; RV798 is deleted of US2-US11; RV7181 is deleted of IRS1-US9; RV7177 is deleted of IRS1-US6; and RV7186 is deleted of IRS1-US11. MHC class I heavy chain down regulation results are from immunoprecipitation experiments (using the heavy chain conformation-independent monoclonal antibody, TP25.99) in which HCMV-infected HFF cells were radiolabeled at late times postinfection. FIG. 10C shows the cation of the two subregions which contain gene(s) which are sufficient for MHC class I heavy chain down regulation. Subregion A contains ORFs US2-US5 (bases 193119-195607 set forth in SEQ ID NO: 1 and subregion B contains ORFs US10 and US11 (bases 199083-200360 set forth in SEQ ID NO: 2).

FIG. 11A-11B are Western Blots of cell lines expressing the HCMV US11 gene. Uninfected human U373-MG astrocytoma cells stably transformed with a US11. expression plasmid were analyzed by Western Blot analysis for MHC class I heavy chain expression FIG. 11A) and for US11 expression (FIG. 11B) using the TP25.99 monoclonal antibody and the US11 polyclonal antisera, respectively.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

A recombinant HCMV mutant called RV670, has been constructed which expresses a marker gene (β-glucuronidase) in place of a group of vital genes. Upon infection of human fibroblast cells with this mutant, it is demonstrated that expression of the major histocompatibility complex (MHC) class I heavy chains are not reduced, as it is when wild-type HCMV infects these cells.

Unlike wild-type HCMV, the present invention's virus does not result in the down regulation of cellular MHC class I heavy chain protein expression. A 7 kb region of the HCMV genome which contains genes which are required for down regulation of heavy chain expression is utilized in the invention.

One skilled in the art will appreciate that efficient antigen processing and presentation is required to activate and expand cytotoxic T-Lymphocyte precursors for an efficient cell mediated immune response. Efficient vital antigen presentation requires the continued expression of MHC class I proteins throughout infection. Infection of cells with RV670 results in continued expression of class I heavy chains.

One skilled in the art will appreciate that the claimed virus (RV670) or another human cytomegalovirus with a deletion of similar genes, can be utilized to produce an effective live vaccine since class I heavy chains are still expressed in RV670-infected cells, as they are in uninfected cells, and therefore vital antigen presentation, for the purpose of initiating a cytotoxic T cell response occurs.

In the present invention, flow cytometry and immunofluorescence experiments confirmed that cell surface expression of class I heavy chains are greatly reduced at late times postinfection in HCMV wild-type strain 8169 infected HFF cells. Radiolabeling-immunoprecipitation experiments indicates that down regulation of newly synthesized MHC class I heavy chains occurs throughout the course of infection, beginning at very early times (3 h) postinfection (FIG. 2C). This reduction has been reported to be at the post-translational level: class I heavy chains have a higher turnover rate in HCMV-infected cells than in uninfected cells (Beersma et al., 1993). Such instability of class I heavy chains results in a reduced cell mediated immune response to HCMV infection since viral peptides will be inefficiently presented. Thus, the reduction in class I heavy chain expression is important in terms of evasion of host's immune system in the establishment of persistent or latent infections by HCMV (Gooding, 1992).

We screened our bank of HCMV mutants which represent 18 ORFs which are dispensable for viral replication in tissue culture for their ability to cause down regulation of MHC class I heavy chains. A 7-kb region of the S component of the HCMV genome, containing ORFs US2-US11 (bases 193119-200360set forth in SEQ ID NO: 3), is clearly shown to contain genes which are required for this phenotype (data summarized in FIG. 10). Within this region, there are two subregions, each of which contain genes sufficient for heavy chain down regulation. Subregion A contains ORFs US2-US5 (bases 193119-195607set forth in SEQ ID NO: 1). It is proposed that US2 and. US3 encode membrane glycoproteins (Chee-et al.,. 1990). US3 is a differentially spliced gene which is expressed throughout the vital replicative cycle and encodes a protein with transcriptional transactivating function (Tenney and Colberg-Poley, 1991; Colberg-Poley et al., 1992; Tenney et al., 1993; Weston, 1988). Several smaller ORFs are also present in this subregion (between the ORFs US3 and US5), but their expression characteristics or functions have not been reported. Gretch and Stinski (1990) reported that there is a 1.0-kb early mRNA transcribed from this region of the HCMV genome, but it was not fine-mapped. It is not yet known which of these genes are involved in heavy chain down regulation.

Subregion B is also sufficient for MHC class I heavy chain reduction contains the US10 and US11 genes (FIG. 10), bases 199083-200360 set forth in SEQ ID NO: 2. However, based on data using HCMV mutant RV670, which expresses wild-type levels of the US10 gene product (Jones et al., manuscript in preparation), US10 expression is not sufficient for down regulation of heavy chain expression (FIG. 2B). Thus, the genetic data implicates the US11 gene product as being required. We have demonstrated that US11 expression is sufficient to cause MHC class I heavy chain down regulation in stably transformed uninfected cells in the absence of other MCNV proteins (FIG. 11). RNA and protein expression from both of these ORFs begins early and proceeds throughout the course of infection (Jones and Muzithras, 1991); US10 and US11 encode glycoproteins of 22-kDa (gpUS10) and 32-kDa, (gpUS11) respectively; both glycoproteins have N-linked sugar residues which are completely endoglycosidase. H sensitive. These glycoproteins are retained in the endoplasmic reticulum or cis golgi. Consistent with this conclusion is the immunofluorescence data in which gpUS11 was not detected on the cell surface, but was detected in the cytoplasm of HCMV-infected cells (FIG. 8). The characteristics of HCMV gpUS11 (as well as gpUS10) are similar to the 25-kDa glycoprotein (E3-19K) encoded from the E3 region of adenovirus type 2. Ad E3-19K is nonessential for vital replication. It has been shown to contain endoglycosidase K-sensitive N-linked sugar residues, be retained in the endoplasmic reticulum, and bind MHC class I heavy chains; thereby preventing their transport to the cell surface 9 (Anderson et al., 19.85; Burgert and Kvist, 1985). In contrast to Ad E3-19K, a direct association between gpUS11 (or gpUS10) and class I heavy chains (i.e. by coimmunoprecipitation) was not detected (data not shown).

The identification of US2-US11 gene region as the region of the HCMV genome required for down regulation of MHC class I heavy chains is significant in several respects. As mentioned above, expression from this region of the genome throughout the course of infection acts to interfere with an effective cell mediated immune response. Surface expression of MHC class I molecules is required for antigen presentation to activate and expand cytotoxic T lymphocyte (CTL) precursors populations (Schwartz, 1985). In addition, they are further required for target recognition by the activated CTLs (Zinkernagel and Doherty, 1980). In MCMV, CTLs against the major immediate-early protein are protective against lethal infection by this virus (Jonjic et al., 1988). However, in HCMV infected individuals, the frequency of CTLs against the analogous HCMV immediate-early protein, IE1, are reported to be extremely rare (Gilbert et al., 1993). Recent studies have shown that IE peptides are more efficiently presented by interferon-γ-treated HCMV-infected cells, than by untreated infected cells (Gilbert et al., 1993). Interferon μ causes increased surface expression of MHC class I proteins. Thus, increasing the expression of class I heavy chains in HCMV-infected cells may be important in the efficient generation of IE-specific CTLs, or CTLs against other important HCMV antigens. A HCMV mutant deleted of the US2-US11 gene region would have this effect since the class I heavy chains are not down regulated when cells are infected with this mutant. Therefore, a deletion of this region of the vital genome is important in the development of an live HCMV vaccine to induce an effective anti-HCMV immune response.

Several years ago it was reported that the HCMV UL18 ORF encoded a protein which resembled MHC class I heavy chains (Beck and Bartell, 1988). It was hypothesized that the down regulation of heavy chains in HCMV-infected cells was due to competition of the UL18 gene product for β2-microglobulin, which effectively prevented the normal association of class I heavy chains and β2-microglobulin (Browne et al., 1990). This hypothesis was essentially dispelled when a HCMV mutant deleted of UL18 retained its ability to down-regulate heavy chain expression (Browne et al., 1992). It remained possible that the UL18 gene product was only one of several HCMV genes whose expression is sufficient for this phenotype. However, the present invention data indicates that only genes within the US2-US11 region are sufficient for class I heavy chain down regulation.

The existence of two independent mechanisms which result in down regulation of MHC class I expression emphasizes the importance of this phenotype for successful infection and persistence in the host. One mechanism may serve as a backup system for the other, but also plausible is that there is cell type specificity for each system. In the case of the HFF cell system, both mechanisms are functional. However, in U373-MG cells' down regulation of heavy chain expression is more dependent on the presence of the subregion A. In that case, there may be qualitative or quantitative differences in cellular proteins which interact with subregion B gene products. A similar situation exists in the herpes simplex virus system. It was recently reported that the 88 amino acid US12 gene product (ICP47) is sufficient for class I heavy chain sequestering in the endoplasmic reticulum (York et al., 1994). However, expression of heavy chains is not affected in herpes simplex virus-infected mouse cells, although ICP47 is expressed in those cells and murine heavy chains are down-regulated when expressed in an HSV-infected human fibroblast system (York et al., 1994).

A pharmaceutical composition may be prepared containing the recombinant HCMV mutant of the present invention in which the genome is devoid of a gene sequence capable of down regulating MHC Class I expression in infected cells. A stabilizer or other appropriate vehicle may be utilized in the pharmaceutical composition.

As discussed earlier, the recombinant HCMV mutant of the present invention which is devoid of the gene sequence capable of down regulating MHC Class I expression may be used in a vaccine for the prevention of cytomegalovirus infections. The vaccine comprises an effective amount of the recombinant HCMV mutant in a pharmaceutically acceptable vehicle. An adjuvant may be optionally added to the vaccine.

A method of immunizing an individual against cytomegalovirus may be carried out by administering to the individual an immunogenic amount of the recombinant HCMV mutant of the present invention which is devoid of the gene sequence capable of down regulating MHC Class I expression.

A method of preventing or reducing susceptibility in an individual to acute cytomegalovirus may be carried out by administering to the individual an immunogenic amount of the recombinant HCMV mutant of the present invention which is devoid of the gene sequence capable of down regulating MHC Class I expression.

Down regulation of MHC Class I expression in a cytomegalovirus infected cell may be controlled by a method having the steps of identifying a gene sequence capable of down regulating the major histocompatibility complex and deleting the identified gene sequence from the cytomegalovirus genome.

As discussed earlier, the gene sequence involved in the MHC Class I heavy chain down regulation can be incorporated into adenovirus vectors or similar virus based gene therapy vectors to minimize the immune response and allow the use of the vectors in gene therapy. One virus based gene therapy vector comprises the gene sequence of the open reading frame of US11. Another virus based gene therapy vector comprises the gene sequences of subregions A and B (open reading frames US2-US5 and US10-US11, respectively).

EXAMPLE 1

Virus and Cells. HCMV strain AD169is obtained from the American Type Culture Collection and propagated according to standard protocols known by those skilled in the art. Human foreskin fibroblast (HFF) cells were isolated in this laboratory and used below passage twenty (Jones and Muzithras, 1991). They were grown in Dulbeccos modified Eagle medium (DMEM) containing 10% fetal bovine serum and 25 mM HEPES.

DNA sequence. The numbering system of Chee et al. (1990) of the HCMV strain AD169 DNA sequence (Genbank accession number X17403) is Used in the present invention.

Plasmids. Plasmids used for creation of HCMV mutants are constructed using the method described previously (Jones et al., 1991; Jones and Muzithras; 1992). Generally, the β-glucuronidase reporter gene is surrounded on each side by 1.5-kb of HCMV sequences which flank the gene(s) to be deleted from the virus. In each case, the plasmid DNA is linearized with a restriction enzyme which cuts within the prokaryotic backbone prior to transfection. The HCMV strain AD169 genomic DNA fragments are derived from either pHind-G, pHind-X, or pXba-P which contain the HindIII-G (bases 176844 to 195837 set forth in SEQ IN NO: 4), -X (bases 195837 to 200856 set forth in SEQ ID NO: 5), and XbaI-P (bases 200391. to 206314 set forth in SEQ ID NO: 6) DNA fragments, respectively (Oram et al., 1982; Jones et al., 1991). pUS7/US3 contains the 1.7-kb PstI-PstI HCMV fragmgnt (bases 194741 to 196447 set forth in SEQ ID NO: 7in pIBI30 vector International Biotechnologies, Inc.!) derived from pHind-G and pHind-X.

To replace HCMV ORFs US11 through IRS1 by β-glucuronidase (i.e. RV7186; FIG. 3), pBgdUS11/IRS1 are constructed. Sequentially, this plasmid contains the 1.8-kb fragment PstI-Xbai fragment (bases 200391 to 202207 set forth in SEQ ID NO: 8; containing US13, US12, and US11 promoter sequences; from pXba-P), β-glucuronidase, a 288-b SV40 fragment containing the early and late polyadenylation signals (from pRcCMV Invitrogen!), and the 1.7-kb NcoI-NcoI fragment (bases 188062 to 189763 set forth in SEQ ID NO: 9; containing J1I to IRL1 sequences; from pHind-G).

To replace HCMV ORFs US11 through US2 by β-glucuronidase (i.e. RV798; FIG. 3), pBgdUS11/US2 are constructed. Sequentially, this plasmid contains the 1.8-kb fragment PstI-XbaI fragment (bases 200391 to 202207 set forth in SEQ ID NO: 8; containing US13, US12, and US11 promoter sequences; from pXba-P), β-glucuronidase, a 255-b fragment containing the US10 polyadenylation signal (bases 199021 to 199276 set forth in SEQ ID NO: 10; from pHind-X), and the 1.3-kb NheI-ApaI fragment (bases 192033 to 193360 set forth in SEQ ID NO: 11; containing C-terminal US2 to IRS1 sequences; from pHind-G).

To replace HCMV ORFs US11 through US6 by β-glucuronidase (i.e. RV35; FIG. 3), pBgdUS11/US6 was constructed. Sequentially, this plasmid contains the 1.8-kb PstI-XbaI fragment (bases 200391 to 202207 set forth in SEQ ID NO: 8; containing US13, US12, and US11 promoter sequences from pXba P), β-glucuronidase, and the 1.5-kb HpaI-SstII fragment (bases 194062 to 195589 set forth in SEQ ID NO: 12; containing C-terminal US6 to US3 sequences; from pHind-G). Replacement of HCMV ORFs US11-US10, or ORF US11 (singly), by β-glucuronidase (i.e. RV67 and RV699, respectively) were described previously (Jones et al., 1991).

To replace HCMV OREs US9 through IRS1 by β-glucuronidase (i.e. RV7181; FIG. 3), pBgdUS9/IRS1 was constructed. Sequentially, this plasmid contains the 1.1-kb SalI-ApaI fragment (bases 199021 to 200171 set forth in SEQ ID NO: 13), the 351-b SV40 early promoter (from pRcCMV), β-glucuronidase, the 288-b SV40 polyadenylation signal fragment, and the 1.7-kb NcoI-NcoI fragment (bases 188062 to 189763 set forth in SEQ ID NO; 9; containing J1I to IRL1 sequences; from pHind-G).

To replace HCMV OREs US6 through IRS1 by β-glucuronidase (i.e. RV7177; FIG. 3), pBgdUS6/IRS1 was constructed. Sequentially, this plasmid contains the 1.7-kb NcoI-NcoI fragment. (bases 188062 to 189763set forth in SEQ ID NO: 9; containing IRL1, JlI, and IRS1 promoter sequences; from pHind-G), β-glucuronidase, the 255-b fragment containing the US10 polyadenylation signal (bases 199021 to 199276 set forth in SEQ ID NO: 10; from pHind-X), and the 1,8-kb BsmI-SauI fragment (bases 196222 to 198030 set forth in SEQ ID NO: 14; containing US7 to C-terminal US9 sequences; from pHind-X).

To replace HCMV OREs US3 and US2 by β-glucuronidase (i.e. RV47; FIG. 3), pBgdUS3/US2 was constructed, Sequentially, this plasmid contains the 1.7-kb PstI-PstI fragment (bases 194741 to 196447 set forth in SEQ ID NO: 7), a 180-b SmaI-HaeIII fragment containing the HSV-1 gH promoter (McKnight, 1980), β-glucuronidase, the 255-b US10 polyadenylation signal fragment, and the 1,.3-kb NheI-ApaI fragment (bases 192033 to 193360 set forth in SEQ ID NO: 11; containing C-terminal US2 to IRS1 sequences; from pHind-G).

To replace HCMV ORE US1 by β-glucuronidase (i.e. RV5122; FIG. 3), pBgdUS1 was constructed. Sequentially, this plasmid contains the 1.8-kb AatII-SstI fragment (bases 190884 to 192648 set forth in SEQ ID NO: 15; containing IRS1 and US1 C-terminal sequences; from pHind-G), a 180-b SmaI-HaeIII fragment containing the HSV-1 gH promoter (McKnight, 1980), β-glucuronidase, the 255-b US10 polyadenylation signal fragment, and the 1.6-kb SphI-SphI fragment (bases 192934 to 194544 set forth in SEQ ID NO: 16; containing US2 and C-terminal US3 sequences; from pHind-G).

To replace HCMV ORF IRS1 by β-glucuronidase (i.e. RV46; FIG. 3), pBgdIRS1 was constructed. Sequentially, this plasmid contains the 1.7-kb NcoI-NcoI fragment (bases 188062 to 189763 set forth in SEQ ID NO: 9; containing IRL1, J1I, and IRS1 promoter sequences; from pHind-G), β-glucuronidase, the 255-b fragment containing the US10 polyadenylation signal (bases 199021 to 199276 set forth in SEQ ID NO: 10; from pHind-X), and the 1.2-kb NarI-XhoI fragment (bases 191830 to 193003set forth in SEQ ID NO: 17; containing C-terminal IRS1 and US1 sequences; from pHind-G). To delete HCMV ORFs US11 through US2 without insertion of a reporter gone (i.e. RV799; FIG. 3), pdUS11/US2 was constructed. Sequentially, this plasmid contains the 1.8-kb fragment PstI-XbaI fragment (bases 200391 to 202207 set forth in SEQ ID NO: 8; containing US13, US12, and US11 promoter sequences; from pXba-P), β-glucuronidase, 65-b NruI-ApaI fragment containing the US10 polyadenylation signal (bases 199021 to 199086 set forth in SEQ ID NO: 18; from pHind-X), and the 1.3 -kb NheI-ApaI fragment (bases 192033 to 199360 set forth in SEQ ID NO: 11; containing C-terminal US2 to IRS1 sequences; from pHind-G).

Isolation of recombinant mutant HCMV. Creation and isolation of recombinant mutant HCMV is done as described previously (Jones et al., 1991; Jones and Muzithras, 1992). HFF cells are split so that they are 70-80% confluent on the day of transfection. The cells are trypsinized and suspended to 5.6×10⁶ cells per ml in DMEM/10% FCS/25 mM HEPES. The DNA is transfected using a modified calcium phosphate co-precipitation technique. 1.5 μg of infectious HCMV DNA and 2.5 μg of linearized plasmid DNA are mixed in the calcium chloride solution (300 μl containing 10 mM Tris pH 7.0/250 mM calcium chloride) and chilled on ice. To initiate the co-precipitation, the DNA is removed from the ice and 300 μl 2×HeBS pH 6.95 (at room temperature; 1×HeBS is 19.2 mM HEPES, 137 mM NaCl, 5 mM KCl, 0.8 mM sodium phosphate, 0.1% dextrose) is added dropwise with gentle mixing. After 1.5 min, the precipitate is placed on ice (to prevent further precipitate from forming). The precipitate is mixed with 3×10⁶ cells (in suspension) and placed in a 82 mm tissue culture plate. After 6 h at 37° C., the media is removed and the cells are shocked with 20% DMSO in 1×HeBS for 2 min. The cells are washed twice with PBS and growth media is added. The media is changed every 4-7 days. After 14 days, vital plaques are observed and the cells are overlaid with 0.5% agarose in DMEM containing 150 μg/ml X-gluc (5-bromo 4-chloro 3-indol 1-glucuronide; Biosynth). Blue plaques (i.e. β-glucuronidase-positive mutant virus plaques) are picked several days after adding the overlay. Recombinant viruses were plaque purified three times. HCMV mutant RV799 is β-glucuronidase-negative and is isolated using a modification of the above procedure. In this case, β-glucuronidase-positive HCMV mutant RV134 is the parent virus (Jones et al., 1991). Thus, RV134 genomic DNA is used instead of wild-type strain AD169 DNA in the transfections. Primary plaques appearing on the primary transfection plates are picked at random and replated on HFF cells. After 10 days, the media is removed and the infected cells are overlaid with X-gluc-containing agarose as described above. In this case, white plaques (β-glucuronidase-negative mutant virus plaques) are picked 4 days later and plaque purified. The proper genomic organization of each of HCMV mutants is verified by DNA blot hybridization analysis as described previously (Jones et al., 1991).

Antibodies. Rabbit polyclonal antisera reactive with HCMV US11 proteins and HCMV UL80 proteins are described previously (Jones et al., 1991; 1994). Murine monoclonal antibodies W6/32, specific for a conformation-dependent epitope on the heavy chain of human MHC class I proteins, and Ber-T9, specific for the human transferrin receptor, are purchased. Murine monoclonal antibody TP25.99 (D'Urso et al., 1991), specific for a conformation-independent epitope on the heavy chain of human MHC class I proteins, is obtained from Dr. S. Ferrone (Department of Microbiology, New York Medical College, Valhalla, N.Y.). Murine monoclonal antibody 9221, Specific for the HCMV IE1 protein, is purchased from Dupont.

Radiolabeling and immunoprecipitation of infected cell proteins. Pulse-Chase radiolabeling is done according to standard protocol (Sambrook et al., 1989). HCMV-infected HFF cells (multiplicity of infection equals five) is pulse-labeled with 200 μCi of ³⁵ S ! methionine and ³⁵ S !cystsine (NEN-DuPont) per ml in methionine/cystsine-free Dulbecco's modified Eagle medium (DMEM) at the indicated time period postinfection. The radioactive media is removed, the cells washed twice in complete DMEM, and chases are done for the indicated time in complete DMEM. Proteins are extracted using triple detergent lysis buffer (Sambrook et al., 1989). The cleared protein extracts (supernatant after centrifugation for 5 min at 15000×g and 4° C.) are retained for immunoprecipitation according to standard protocol (Sambrook et al., 1989). Proteins binding to antibodies are pelleted using protein A sepharose (Pharmacia). For immunoprecipitations of the human transferrin receptor, rabbit anti-mouse IgG (Pierce) are added prior to protein A sepharose. The washed immunoprecipitates were boiled in the presence of 2-mercaptoethanol and electrophoresed in denaturing polyacrylamide gels. The gels are fixed and soaked in 1M sodium salicylate fluor (Sambrook et al, 1989) prior to drying and autoradiography.

Immunofluorescence. Immunofluorescence assays are done according to standard protocol (Harlow, 1989). All procedures are done in 60 mm tissue culture plates. Briefly, infected or uninfected HFF cells were fixed with 4% paraformaldehyde and permeabilized with 0.2% "TRITON X-100" (where indicated). After adding 3% bovine serum albumin in phosphate-buffered saline, the cells are held overnight at 4° C. The cells are treated sequentially with the following antisera, each for 30 min at room temperature: 10% HCMV-negative human serum (to block any Fc receptors); the indicated primary antibody; and FITC-conjugated anti-mouse or anti-rabbit IgG, as appropriate.

EXAMPLE 2

Class I down regulation in HCMV wild-type-infected human fibroblasts. We sought to ascertain the timing and nature of MHC class I heavy chain down regulation in the present invention's human foreskin fibroblast (HFF) cell culture system. By flow cytometry, HCMV strain AD169 wild-type-infected HFF cells are significantly reduced in the expression of class I heavy chains on their cell surface at late times postinfection (i.e. 72 h) using the conformation-dependent class I monoclonal antibody W6/32 (FIG. 1). In western analyses using the conformation-independent class I monoclonal antibody (TP25.99), it is demonstrated that the steady state level of class I protein is also reduced at late times postinfection (FIG. 2A). Because vital peptides are presented at the cell surface by class I complexes assembled after infection, we sought to assess the status of class I proteins synthesized at various times postinfection by immunoprecipitation of metabolically radiolabeled proteins. As shown in FIG. 2B, reduction in expression of class I heavy chains is detected both in the presence and absence of the viral DNA synthesis inhibitor, phosphonoformate. This indicates that vital immediate-early or early gene functions are sufficient for heavy chain reduction. In addition, it is demonstrated that heavy chain down regulation was detected at very early times postinfection: 3 h (FIG. 2C). Since this effect is observed using the conformation-independent antibody, the reduction reflects overall levels of newly synthesized heavy chains.

Screening of HCMV mutants for the loss of MHC class I down regulation. Several previously constructed HCMV deletion mutants, representing 18 nonessential ORFs (UL33, UL81, IRS1, US1-US13, US27-US28, and TRS1), are screened for heavy chain expression by flow cytometry and immunoprecipitation analyses. Only RV670, a mutant deleted of a 9-kb region within the S component of the HCMV genome (Jones and Muzithras, 1992), does not retain the wild-type down regulation phenotype (FIG. 4A). This mutant is deleted of at least. 11 ORFs, IRS1 through US11 (except for US10), which includes the US6 family of genes (US6-US11) which putatively encode glycoproteins (Chee et al., 1990). To confirm this observation, two additional independently derived mutants which have the same deletion as RV670 and a new mutant, RV7186, deleted of the entire IRS1-US11 region (FIG. 3) are tested. Each is phenotypically identical to RV670 and stably expressed class I heavy chains. Previously, we constructed HCMV mutants deleted of US6 family ORFs, either individually or in groups (Jones and Muzithras, 1992), and similar deletion mutants within the adjacent IRS1-US3 region. By immunoprecipitation using the conformation-independent antibody, all of these mutants are shown to retain the ability to down regulate class I heavy chains (FIG. 4A) at late times postinfection in HFF cells. Control experiments indicate that radiolabeling is equivalent between the different infected cell cultures (FIG. 4B) and that infection proceeded to late times equally, as judged by pp65 (FIG. 4B) and UL80 protein (FIG. 4C) expression. These data indicate: (i) that more than one vital gene is sufficient for the reduction in class I heavy chains; or (ii) gene(s) between US3 US6, deleted in RV670 and RV7186 but not the other mutants, is required for the phenotype.

Identification of a 7-kb region of the HCMV genome required for MHC class I down regulation. To further localize the region containing gene(s) involved in MHC class I heavy chain down regulation, additional HCMV replacement mutants containing deletions of multiple genes within the IRS1-US11 gene region are created (FIG. 3). One of these mutants, RV798, is deleted of genes from US2-US11. In HFF cells infected by RV798 and analyzed at late times postinfection, MHC class I heavy chains are not down-regulated as they are in wild-type strain AD169-infected cells (FIG. 4A); in fact, a slight stimulation is observed. Several independently-derived deletion mutants identical to RV798 were examined similarly: all lacked the ability to down regulate class I heavy chains. To further confirm that the 7-kb HCMV US2-US11 region contains the gene(s) required for heavy chain down regulation, mutant RV799 is constructed which has the identical US2-US11 deletion as RV798, but is created by a different strategy. RV798 is derived from wild-type strain AD169 by inserting a β-glucuronidase marker gene in the place of US2-US11. In contrast, the parent of RV799 is RV134, a mutant which is β-glucuronidase-positive since it has a β-glucuronidase expression cassette inserted within the US9-US10 intergenic region (Jones et al., 1991). To create RV799, a plasmid is designed which upon recombination with the RV134 genome would simultaneously delete US2-US11 and the β-glucuronidase expression cassette (FIG. 3). The proper RV799 HCMV mutant is isolated as a white plaque in the presence of the β-glucuronidase substrate, since it β-glucuronidase-negative. RV799, but not the RV134 parent, is phenotypically identical to RV798 (FIG. 5) Thus, since RV798 and RV799 are created by different strategies using parents which retained the ability to down regulate MHC class I heavy chains, this confirms that the gene(s) required for the phenotype are located within the 7-kb US2-US11 region (bases 193119-200360 set forth in SEQ ID NO: 3). To determine whether the proper surface expression of class I heavy chains occurred at late times postinfection with either RV798 or RV799, immunofluorescence assays are done. Using either the conformation-dependent (W6/32) or conformation-independent (TP25.99) monoclonal antibodies, surface expression of MHC class I heavy chains is detected in uninfected and RV798- and RV799-infected HFF cells, but not wild-type AD169-infected HFF cells. Proper maturation of class I heavy chains in uninfected cells yields endoglycosidase H resistant molecules. In contrast, class I heavy chains synthesized in AD169-infected cells are reported to be entirely endoglycosidase H sensitive (Beersma et al., 1993). As shown in FIG. 6, class I heavy chains synthesized in RV798-infected HFF cells, either at early or late times postinfection, are converted to the mature endoglycosidase H-resistant format a rate similar to those synthesized in uninfected cells. Taken together, these data indicate that MHC class I synthesis, processing, and surface expression are not impaired in cells infected with these HCMV mutants. Furthermore, the results indicate that the 7-kb region containing US2-US11 genes contain one or more genes required for heavy chain down regulation by HCMV.

Two subregions within the US2-US11 gene region contain genes which are involved in class I heavy chain down regulation. The region of the HCMV genome deleted in RV35 is from US6-US11, and US2-US11 in RV798 (FIG. 3). In RV35-infected HFF cells, MHC class I heavy chains are down regulated, but in RV798-infected cells they are not (FIG. 4A). This data indicates that one or more genes involved in heavy chain down regulation maps within the 2-kb subregion from ORF US2 through US5 (subregion A; bases 193119-195607 set forth in SEQ ID NO: 1). To determine if this 2-kb subregion is required for class I heavy chain down regulation, HCMV replacement mutants RV7181 and RV7177 are examined. HCMV ORFs IRS1-US9 and IRS1-US6 are deleted, respectively, in these mutants; hence, subregion A is absent from both mutants. Experiments in infected HFF cells at late times postinfection indicates that both mutants retained the ability to efficiently down regulate class I heavy gene expression (FIG. 7). Therefore, when present in the HCMV genome, gene(s) within subregion A are sufficient for reduction of MHC expression (e.g. RV35), although their presence is not required for the phenotype. Furthermore, the cumulative data indicate that there are no HCMV genes within the identified 7-kb US2-US11 region (i.e. the region deleted in RV798) which are absolutely required for efficient heavy chain down regulation in infected HFF cells, suggesting that gene(s) from another portion of the US2-US11 gene region are also sufficient for the phenotype at late times postinfection.

Evidence indicating that the US11 gene product is involved in MBC class I heavy chain down regulation. In HFF cells infected with mutant RV7181, deleted from IRS1-US9 (FIG. 3), MHC class I heavy chain expression is down regulated, in contrast to RV798-infected HFF cells (FIG. 7). This data suggests that a second subregion (subregion B), comprised of the US10 and US11 genes (bases 199083-200360 set forth in SEQ ID NO: 2), is involved in reduction of heavy chain expression. However, the expression of US10 from the context of the HCMV genome is not sufficient for heavy chain down regulation. HCMV mutant RV670 expresses US10 at steady-state levels similar to wild-type and is deleted of all of the other ORFs in the 7-kb US2-US11 gene region, but it does not cause down regulation of MGC class I heavy chains in infected HFF cells (FIGS. 2B and 4A).

US11 encodes a 32-kDa glycoprotein (gpUS11) containing N-linked, but not O-linked, carbohydrates which are completely sensitive to endoglycosidase H, indicating that the sugars are in the high mannose form. gpUS11 is detected throughout infection, beginning at very early times (i.e. 3 h) and continuing through late times postinfection. However, levels of gpUS11 in the infected cell are most abundant at approximately 8 h postinfection. To determine its location in the infected cell, rabbit polyclonal antisera (Jones and Muzithras, 1991) is used in immunofluorescence assays of wild-type strain AD169-infected cells. Uninfected and RV699-infected HFF cells are used as negative controls. RV699 is an HCMV mutant which is isogeneic with AD169, except for a deletion of the US11 ORF (Jones et al., 1991). In cells fixed and permeabilized at 8 h postinfection, cytoplasmic fluorescence which obscured definition of the nucleus is observed in AD169-infected HFF cells, but not in either negative control cells (FIG. 8). In general, the specific fluorescence is more intense in the perinuclear area. There is no specific fluorescence detected in non-permeabilized cells (FIG. 8). The fluorescence and endoglycosidase-H sensitivity data indicate that gpUS11 is not a cell surface glycoprotein. From the translated DNA sequence, gpUS11 is predicted to have hydrophobic domain near its N- and C-termini (Weston and Bartell, 1986) which are putative signal sequence and transmembrane domain, respectively. Thus, gpUS11 is associated with intracytoplasmic membranes, possibly the endoplasmic reticulum.

Down regulation of MHC class I expression at early times postinfection by HCMV mutants. MHC class I expression in wild-type strain AD169-infected cells are shown to begin at very early times postinfection (FIG. 2C). To determine if any of the mutants are deficient for this early down regulation, inununoprecipitation experiments are performed using extracts from infected HFF cells radiolabeled from 6-10 h postinfection. The level of class I heavy chains are reduced during this early period postinfection in HFF cells with each of the mutants, except for RV798, the mutant deleted of the entire 7-kb US2-US11 region (FIG. 9A). Control experiments demonstrated that the different mutant-infected cells are equally infected and radiolabeled (FIG. 9B and D). Expression of another cellular glycoprotein, the transferrin receptor, is not differentially affected by the various mutants (FIG. 9C). Thus, genes required for heavy chain down regulation at early times postinfection are the same as those necessary for reduction at late times postinfection. Moreover, expression of gene(s) from either subregion identified to be involved in down regulation of heavy chain expression at late times postinfection are sufficient for reduction at very early times postinfection.

EXAMPLE 3

Recombinant HCMV (RV798) Vaccine Preparation. HCMV vaccines are prepared using a method described previously (Elek and Stern, 1974). HCMV mutant RV798 is grown on MRC-5 human diploid lung fibroblasts (CCL171 American Type Culture Collection!) or human foreskin fibroblasts (MRHF BioWhittaker!). Cells are infected at a multiplicity of infection equal to one in Dulbecco's modified Eagle medium (DMEM) containing 5% calf serum and 5% fetal calf serum. After 24 h, the medium is removed and the cells washed three times with either Hank's balanced salt solution or Dulbecco's phosphate-buffered saline. Fresh DMEM medium without serum is added; the infected cells are incubated 4 days after the appearance of late vital cytopathic effect (usually 7 days postinfection). After a preclearing centrifugation step (6,000×gravity for 20 main at 18° C.), cell-free virus is pelleted by centrifugation at 15,500×gravity for 1 h at 18° C. The pelleted virus is resuspended in Dulbecco's phosphate-buffered saline containing 25% sorbitol and stored in aliquots at -70° C. The titer of RV798 vaccine stock is determined using standard procedures on human foreskin fibroblasts (Wentwork and French, 1970). The vaccine is administered by subcutaneous inoculation of approximately 10³ -10⁷ plaque forming units into the deltoid region of the upper arm, as described previously (Elek and Stern, 1974; Gehrz et al., 1980; Starr et al., 1981).

EXAMPLE 4

gpUS11 is sufficient for down regulation of MHC class I heavy chains. To determine if the US11 gene product, in the absence of any other vital gene products, is capable of causing heavy chain down regulation, the US11 coding region (bases 199716 to 200360 set forth in SEQ ID NO: 19 Chee et al., 1990!) and some non-coding flanking sequences, encompassing bases 199683 to 200391 set forth in SEQ ID NO: 20, are cloned into a eukaryotic expression plasmid under the transcriptional control of the constitutive HCMV major immediate-early promoter-enhancer. Human U373-MG astrocytoma cells (HTB 17 American Type Culture Collection!) are transfected with this plasmid (Sambrook et al, 1989) and stably transformed cells are selected in the presence of 0.375 μg/ml of puromycin, since the plasmid also encodes for the prokaryotic puromycin resistance gene. Clones are picked and expanded into cell lines. Those expressing gpUS11 are identified by western blot analysis; different cell lines expressed varying amounts of US11. MHC class I heavy chain expression in these cell lines is analyzed in a similar fashion. As shown in FIG. 11, expression of US11 is inversely correlated with the expression of class I heavy chains. These data prove that expression of HCMV US11 is sufficient for the down regulation of MHC class I heavy chain expression, in the absence of any other viral gene products.

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    __________________________________________________________________________     SEQUENCE LISTING                                                               (1) GENERAL INFORMATION:                                                       (iii) NUMBER OF SEQUENCES: 20                                                  (2) INFORMATION FOR SEQ ID NO:1:                                               (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 2489 base pairs                                                    (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1:                                        GCACACGAAAAACCGCATCCACATCATAGACAAGTTACAGTCCACAGTCACATACACGAT60                 AAACAATACCAACAGGGTAATGTTTATGGAGTAAAACACTATTGTCCAGGCCACATGCGT120                GTATGACTTCCGCACCATCCCGTACTGCATGTTCCACATGTACGCGCTAGACGTGTAATC180                CACTCGCAGTTCGGGGACGCAACGCAGCCAGATCACATCCCCTTGCAGTACCAGACGCAG240                GGCTAGCGTCTCGAAGATCGGCATCACATCTAAGTTCCGCACGTTCCACTTTAACGACTC300                CCCGGGAACGAACTCCACGTCGTCGGCGTGTACGTACAGGTTCTCTCCCACGCCGCCATA360                ATCGGCCTTCGGATCGAAGACGAACCGACTCATGTTGCCCACGATGCTCCCCCGAGCAAA420                CAACTTGCCGTTGTCAATGTAGCACCGGTTGTCCTCGATTTGAAACCAGGGATGCTTGGC480                CGTGGACTTCCAGGGCCGGAGCGCGTCTTCCCCGGCTTTAGTGATTCCATCGGGCAGGCG540                GATCAAGGGACCCATGGAGGTCCAAAGACCCACCCAGGCTTTCCAGAGATTGTTCATGGT600                GAAACAGCGTGTGGACTGTACGCTCTTTCCCAATTTATATCCCAGAGTAGTGACGTGAGC660                CCAGCCACCTCCCAGATTCCTGACGTTTTGGTTGTCTTTCCTGCCAATTCCTCCCGTAAA720                CTTATGATTATCCTAGCCCATTCCCGATAAAAATACACGGAGACAGTAGATAGAGTTACG780                AATAAACCGGTTTATTTATTCAAGTGTCTCAGGAGATTATTGAACGAGCGTGGATACCAC840                GCCGTCGTCAGTTCATGGTGGCATTGAGCAGCCATAGCACCAGAGTCCCGGCGCCCGGTA900                TCAGACACGCTGACCTACCGGGCGCCTTCGAGTCCGTACCCCGCGGCCTGGGTGTTAGAG960                TCCGTACCTTGCAGCCCAGGTAGGTTTCAGGTACCAGCTGGTTCGTACCTGTTAAATAAA1020               TCGCAGACGGGCGCTCACCCCTACGGTCAGGAGCACAAGAACAACCAGAGAGAACAGATA1080               TACGAGCAGGGTTCTGAACAGCAGACCCCAATTGTCGTCTCTCATGCTTCGCTGAAGGTA1140               CCAGTTGATGGTCTGAGAGCTATAGTCCATCCTCACCTGAGGAACACACGCGGCATATTT1200               CTTGGGGTCTCCCCACCTCGTAGACAACGTGATGTCCACCATATCCACGGTGTGCGTCAC1260               CGGGTGCCCACCGATGTTCCACTCGAAATAGGCTCCGCGCTCATCATGGTGGTACTGCTC1320               ACCGGACACCTGCAGTCTGTCCATGTAAGATTGAGAGACGATACCCACGTTCACAAAGTG1380               TTTCTCGGTGAAGTTGCCCGACATCCTCCCCTTGAAGTACAGCATGCCCATATGGAACCA1440               GCATTGGTTCTCCTCCACTCGAAAGTGGGCCGATCTGATCTCCGATACCACCACATCCAG1500               GGGCCGGGGCACCGAGTCCGCGAGTCTCAGGAACAAGACGGCCAGGATCGCGAGCACCAA1560               CACCGGCTTCATGGCTCCGAAGGTCCGCTGCTCGGCTCCGCTCACCGCTCCGGTCTGGCT1620               GCAGCAGTGCTTCGCTGAGAAGTAGCGTGTGGACTGAACGGTGTTTTTGAATATATAGCG1680               TTTCTTGGTGACGTTGTTTCCCCTACGTAGTAGGCAACTACGTGCCAAAAGAGGCGTTAC1740               GGTACTTTCCGTACTGGGATTTCCAAACCGGGACTTTCCACACGGCGGTTTCAACACCGG1800               GACTTTTCACACGGTGATTTCGGCACCGGGACTTTCCGCACGGCGGTTTCGCCACCGCTG1860               ACGTTCTCATCGCCGCCCACGTCAACGGTGGCGACACCGTACTTTCCCATGCGGTTTATA1920               AACGTCAAGAGTCACGTCAGTCGCCCACCCCCATTACACGGCGATATCCCGATAGGGCAT1980               GAGGGGACCCGGGTGTCGCGACATGTCGACGACAGGTGCGGATTAGTGGTCGTGTCGCGA2040               CATGGACGTGCAGGGGGATGTCTGTCGCGATAGAGTTGATGTGACAGCCCGCTACACCTC2100               TCTGTCGCGACATGCATACACAACGGGCCGGCTTGTCGGCGATTGTCGCGACATATCGTT2160               ATCAGTTAGCGACCGGAGTTGTCTATCGCGACATATCGTCGACTATCGCGACAGAAAAAA2220               TACCGTTCGTAGAGAATGCCGTGTTGAAGGAACGCGCTTTTATTGAGACGATAAAACAGC2280               ATCAGGAGCCACAACGTCGAATCCCACGTCCAGTCGATTCGTATGTTATGCTGCACAGCA2340               ATGCTAGAATAACAACCAGCAGGGTAATCCCGCAACATAAATACAAAGTCACAGCGAAGA2400               ATCCGTGTCGTTCTATCAAGCGAAACGCGTTCCAAACGGCCCCGTCACAGACGCAGTTAT2460               TCATAAGCGTTAACAACCGGTGGCTAGGA2489                                              (2) INFORMATION FOR SEQ ID NO:2:                                               (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 1278 base pairs                                                    (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2:                                        TTCGCGAGGTGGATAATAACCGCATATCAGGAGGAGGGATCGGGTGATGACGCAGGCCCC60                 GCAGAACAGTCCGAAATAAATTTTTAGTATTGCCCCATAGTCGCCTAGATACCAGAGGTA120                CGTTAAGTTCATCAAAACGCCCATCGGCGTCCCGGAATCGTATACCGGGCACACGAAGCG180                TTCATAACAATCCCGGGAGGCGAGTGTTAGGGTAGCAGAGTAGTTTCGGGGTCGGTTTCC240                TTCCGGCGACGACAGTTCCGTGGGCAGCAGAATGTACAGCGCCTCGGTAGCTGTCGCGGT300                GCCTTCCACGAGGATGGGCTGCCGGTGCCTTTCGTGATTTTCCCCGTCGTGTAGCCAAGC360                CGAGGCCCGCAAAGTCTTAGGCGAGGGGAATTGTCCATAGAGTTTCACCGCACCCTTCAG420                TACATGGTTCTGAATAACACAGCCGCACGTGAAGTAGGTAGGTTCTCTCGTCTCCTCCGT480                GGCTGCCGCCACCACTCCCAGCCACCACAACAGGCAGATCGCCAGAGGGTTCCGGAGGCT540                TCCCCGGCGTAGCATGGTTTTGGGTTAAAGCAAAAAGTCTGGTGAGTCGTTTCCGAGCGA600                CTCGAGATGCACTCCGCTTCAGTCTATATATCACCACTGGTCCGAAAACATCCAGGGAAA660                ATGTCGGTGCAGCCAACCTTTCACATACAGCCCCCAAAACACTTGAATCACTGCCACCAT720                CATCAGCGTATACTGCGCCGACTTAATCGTGAGCGCGTAGTACGCCATTAGACGGCGATC780                TTCGAACAATAGTCGTTCGATGTCCTCTAACGAGCTCCACAGGGGAACCCAAGGCACGAG840                GCACCGGGGTTCGCACTCTACATAATAAGTTTGGCATTGGTGGCAGGGGGAAAAGTAGAA900                CAACACGAGTTTTGTGCGTTGGGGAACACGATAGTCCCGGAGCCAGTAGCGTTTTGCGAC960                GAGGCTTTCGGAGACGTCCTCCACCGGCGTCGGCACTCGATCCGCGTAGCCCTCCAGCGT1020               CTGGTAGTACACCCGGGGTGTCGGCGTGGGCACGGACAGGTTCCCGCGCAGGGTCCACAG1080               AGCCTCCAGTCGACCGCCCGATCGGAGCACGCAGCGCGCCTCGGAATACTCTACTCGGTA1140               CTCCGAAACATCGGACAGAGGCGGTAACGGCTCCGTCTCCACCAAGGGCGGAGGTTCATC1200               GAAAAGAGTCAAGGATAATTCAGGCATACTACCCGCGACCGGGGCCCAGAGGGCTAGAAT1260               AAGCATTACAAGGTTCAT1278                                                         (2) INFORMATION FOR SEQ ID NO:3:                                               (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 7242 base pairs                                                    (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3:                                        GCACACGAAAAACCGCATCCACATCATAGACAAGTTACAGTCCACAGTCACATACACGAT60                 AAACAATACCAACAGGGTAATGTTTATGGAGTAAAACACTATTGTCCAGGCCACATGCGT120                GTATGACTTCCGCACCATCCCGTACTGCATGTTCCACATGTACGCGCTAGACGTGTAATC180                CACTCGCAGTTCGGGGACGCAACGCAGCCAGATCACATCCCCTTGCAGTACCAGACGCAG240                GGCTAGCGTCTCGAAGATCGGCATCACATCTAAGTTCCGCACGTTCCACTTTAACGACTC300                CCCGGGAACGAACTCCACGTCGTCGGCGTGTACGTACAGGTTCTCTCCCACGCCGCCATA360                ATCGGCCTTCGGATCGAAGACGAACCGACTCATGTTGCCCACGATGCTCCCCCGAGCAAA420                CAACTTGCCGTTGTCAATGTAGCACCGGTTGTCCTCGATTTGAAACCAGGGATGCTTGGC480                CGTGGACTTCCAGGGCCGGAGCGCGTCTTCCCCGGCTTTAGTGATTCCATCGGGCAGGCG540                GATCAAGGGACCCATGGAGGTCCAAAGACCCACCCAGGCTTTCCAGAGATTGTTCATGGT600                GAAACAGCGTGTGGACTGTACGCTCTTTCCCAATTTATATCCCAGAGTAGTGACGTGAGC660                CCAGCCACCTCCCAGATTCCTGACGTTTTGGTTGTCTTTCCTGCCAATTCCTCCCGTAAA720                CTTATGATTATCCTAGCCCATTCCCGATAAAAATACACGGAGACAGTAGATAGAGTTACG780                AATAAACCGGTTTATTTATTCAAGTGTCTCAGGAGATTATTGAACGAGCGTGGATACCAC840                GCCGTCGTCAGTTCATGGTGGCATTGAGCAGCCATAGCACCAGAGTCCCGGCGCCCGGTA900                TCAGACACGCTGACCTACCGGGCGCCTTCGAGTCCGTACCCCGCGGCCTGGGTGTTAGAG960                TCCGTACCTTGCAGCCCAGGTAGGTTTCAGGTACCAGCTGGTTCGTACCTGTTAAATAAA1020               TCGCAGACGGGCGCTCACCCCTACGGTCAGGAGCACAAGAACAACCAGAGAGAACAGATA1080               TACGAGCAGGGTTCTGAACAGCAGACCCCAATTGTCGTCTCTCATGCTTCGCTGAAGGTA1140               CCAGTTGATGGTCTGAGAGCTATAGTCCATCCTCACCTGAGGAACACACGCGGCATATTT1200               CTTGGGGTCTCCCCACCTCGTAGACAACGTGATGTCCACCATATCCACGGTGTGCGTCAC1260               CGGGTGCCCACCGATGTTCCACTCGAAATAGGCTCCGCGCTCATCATGGTGGTACTGCTC1320               ACCGGACACCTGCAGTCTGTCCATGTAAGATTGAGAGACGATACCCACGTTCACAAAGTG1380               TTTCTCGGTGAAGTTGCCCGACATCCTCCCCTTGAAGTACAGCATGCCCATATGGAACCA1440               GCATTGGTTCTCCTCCACTCGAAAGTGGGCCGATCTGATCTCCGATACCACCACATCCAG1500               GGGCCGGGGCACCGAGTCCGCGAGTCTCAGGAACAAGACGGCCAGGATCGCGAGCACCAA1560               CACCGGCTTCATGGCTCCGAAGGTCCGCTGCTCGGCTCCGCTCACCGCTCCGGTCTGGCT1620               GCAGCAGTGCTTCGCTGAGAAGTAGCGTGTGGACTGAACGGTGTTTTTGAATATATAGCG1680               TTTCTTGGTGACGTTGTTTCCCCTACGTAGTAGGCAACTACGTGCCAAAAGAGGCGTTAC1740               GGTACTTTCCGTACTGGGATTTCCAAACCGGGACTTTCCACACGGCGGTTTCAACACCGG1800               GACTTTTCACACGGTGATTTCGGCACCGGGACTTTCCGCACGGCGGTTTCGCCACCGCTG1860               ACGTTCTCATCGCCGCCCACGTCAACGGTGGCGACACCGTACTTTCCCATGCGGTTTATA1920               AACGTCAAGAGTCACGTCAGTCGCCCACCCCCATTACACGGCGATATCCCGATAGGGCAT1980               GAGGGGACCCGGGTGTCGCGACATGTCGACGACAGGTGCGGATTAGTGGTCGTGTCGCGA2040               CATGGACGTGCAGGGGGATGTCTGTCGCGATAGAGTTGATGTGACAGCCCGCTACACCTC2100               TCTGTCGCGACATGCATACACAACGGGCCGGCTTGTCGGCGATTGTCGCGACATATCGTT2160               ATCAGTTAGCGACCGGAGTTGTCTATCGCGACATATCGTCGACTATCGCGACAGAAAAAA2220               TACCGTTCGTAGAGAATGCCGTGTTGAAGGAACGCGCTTTTATTGAGACGATAAAACAGC2280               ATCAGGAGCCACAACGTCGAATCCCACGTCCAGTCGATTCGTATGTTATGCTGCACAGCA2340               ATGCTAGAATAACAACCAGCAGGGTAATCCCGCAACATAAATACAAAGTCACAGCGAAGA2400               ATCCGTGTCGTTCTATCAAGCGAAACGCGTTCCAAACGGCCCCGTCACAGACGCAGTTAT2460               TCATAAGCGTTAACAACCGGTGGCTAGGATGAATATCCAAATCACAGGGCAGTAGCCGAC2520               GGACTCGTTGACAGGTCAGCCTACCCTCAAGGTTCCTATCGTTCGGACGGGATTTGTGCG2580               TTTTAGGCCTCTTTTTCGCCGCCTGCAAGCATTGGTGCGCAAAGTCCTCACCCAGCTGTT2640               TCCAGCTATCATCTGCATCTGTGCAGTCCCCTGTATCGTTGTAACAAACGGGTCTGTGCG2700               ACTTCGTTCTCGGAACACAAGCTTGTTGTCGCGGAGACAGAGAGAGAAGGGTTTTCGGGT2760               CACGCGAAGACCGCTCACCGGGGGTCGGCAACGCACACATCAACAGAAAACCGAGACGAA2820               TCAAGAGATCCATAGTGAAGGAGTGATATCGACGTGCTTACGAAACGGCGATTATATATG2880               TTCTCAACAATACCGCCCTACGTTGTATGATGTAACGTGTGACGTGAGTCTGATCCAACA2940               CTGAACGCTTTCGTCGTGTTTTTCATGCAGCTTTTACAGACCATGACAAGCCTGACGAGA3000               GCGTTCATCGGGGCATGAAGTACGCATTACACAAACTCCATATATTTGTTACGATAGAAT3060               ACGGAACGGAGGAGGCTTTCGCCACACCTATCCTGAAAGCGTTGCATTCTTTATGATAGG3120               TGTGACGATGTCTTTACCATTCCCACGGCTGCTTTGCGTGATGATGACATTCATCATGTA3180               TTTCCATTCACACATACCTTTTGTGCATACGGTTTATATATGACCATCCACGCTTATAAC3240               GAACCTAACAGTTTATTAGCCCTTGACAGGATAGGTCAAAAGATTATATGTAGGTTTTCC3300               GGTAAACCGAATTGTGATATTTCTCTGCAGGAAATAGAACAGCCTGGTACCTATAAAACG3360               GACAATGCAGTACTGTAGCAGCGTAACCAAGTAGGTCCACATGAACACGTACAAAATTAT3420               GGTAAGCCATCGTTTTTCATACCACAGCCTGTAGCTGTCGTACATGAATGAGGACGGTCG3480               AGGAACCCAGGGTAGTTGTAATTGGGGGCGACATTCGTACTGTCCAGAAGACAATTGCAC3540               GGGTTTCAGTGAGATGAGTACTTTAGCGATGTCGGCGGGGGCGCTACGTTTCACCGTGAC3600               GGTGAGAACTTGACCGTCGTTTTGTATTTCATGAGGCACGTTATACAAGCCACTGGTATC3660               ATGAAGGATGACCTCTGATGCGATGTGAGGATTAAATTGTCCCTCAAACCGCCAAACGCT3720               GGTCATGTTTCCACCGTCAATTACGCAGCTGACGGTGTGAGATACCACGATGTTGGACTT3780               AGGTTTGGGGGCTAATTGCCTTTTTACAAATTCCCTTCTGTATTGCAGGTCCTGCTGCCA3840               CTGCTTTTCCGTGCGGAAAGTCGCCATGTCTTCCACACGTGTGGCGACGATAGACGCCAC3900               CAAGGTAGCTACCAGAAGCAGCTGGATCCGCATGGCATTACCGTATGTCAATTAGAAAGT3960               TGAGCGGACACGGTTATCGTTCCTGGCGGATATAAGTATATAAACGCGAGTTAGCCTTTC4020               CCGTCCGTTTTGTACACCCGTTCCCCACACAAATGACGAATACGACCTTTTTTTTTATAA4080               AAATAAACCACGTGTATTATATAAAAACATTTACATAGAAAAGAGACACACGGATCAACA4140               TAAGGACTTTTCACACTTTTGGGGTACACAGGCGTGCCACCGCAGATAGTAAGCGCTGGA4200               TACACGGTACACAGTCCTGGCCAGCACGTATCCCAACAGCAGCACCATCGCCATACAGAT4260               GGCGATCACGACCCCGAGCTCTAAGTGTCTGTATTCATAGTGTAGTCGCCGCAGGTTATC4320               CACTGAATTCCCGTAACTGAAATAACGTATATGGTACCGAGGCTGGCACCACATGGGTTT4380               GCATTTGGTGCACGGCACCAAATGCAGAGTGAGATGGTCCAAGTCCGTGGGCACCCACTG4440               GCGCAAACGGAATACGGCTTCGGTGGTCTCCACGAGGCACTCCGGGGCGTGCAGACGGCC4500               CCACTTTCGTCCGCGACGGCCCGACCAGCCGACCCGAGCCACTATCCCTTTCTCGGGATA4560               GAACGTACCCTGTACACGCCACACAGCGTCCAACACGCCGTCCTTGACGACGCAGCTGGC4620               CTGATAGCTGGACACGTTGTTAAGCGGCGGAAAGCGAAACTGACGTGCCGGCGGAGCCAC4680               ATAGTTCGGTTCACCGTGTTGTCGCGGTTCGTCCTCCCTATAGTAATAGTAGTCGTCGTC4740               CTCATAGGGGTTGCCGGCGTGAGCCAGCGTTACCCAACAGCAGCCCAGGCCGACGAGGAG4800               GCGCAGCCACCGCCTCATGGCGGCTTCGCCAGTCAATCGTCTTTAGCCTCTTCTTCCCGT4860               GAGGTCCTTCCGGTGGCGCGGTGCCGACCTCGGACCCAGGGACGTATCCACCTCAGGTAC4920               ACACAGCAGGCTACCTGGACACCGAAGCTGAACAAGGCTACGTGTTTCACAAACTGCACC4980               AGTACCACATAGAGGAATGTCAGGTAGCGTCTCTCCGCAAACAGCCGTTCCAAGTCTGAG5040               GGCGTTACCCGCAGCGGCAACCAGGGCAGCCTGGACGCCGGCCGGCAATGGAGCACGCTC5100               CGGTTACAGGCACTGCAGGGGTAAACGGTTAACATCACGTAAGAGAGTCGTGCGTCCACC5160               TGTGGGAGCTCAGTTTCGTAACGTAGAGCCCCGTCATTTTCCAGCTGGGGTGCGCCGACC5220               TTGAAATGGGTCGCGCTCCGCTCGTTACCCCAGGTGCCGTAGGCTCTCGGGGCCGTATCG5280               GAGAAGTTGCCACGCACAAGCCAGGCGGCCACGAGTACCCCGTGCTGGACGTAACATTCG5340               GACACGGAACTGGAGACACGGTAGCCGGACACGTCCCCAAACCCGCGAGGGTACTGGGGC5400               AGACGGACGGACTTGCTATTTGACAACGGACAGATACGAGACGACGAGGACGCAGACGAC5460               TCGTCGCTGGACCACGACAACCGGAGCGACTCCTTGGAGCGGCTCGAGAGTACACTTACT5520               GCGATCAGACACCAGTGCCAGAAGAAGGAACAGGTGGACGGGGACCACAGGATCATAGCC5580               GCCGGCACCGCGGCCGGCCGCAGGAAGCCGCCCGGCGCGTCGTCTGTGTGCGGGAGCCGA5640               AACACCGTGCCTCTTTATATCGTCCCGACGTGACGCGAGTATTACGTGTCAGGGGAAACC5700               CCCGTCACGACGAACGTGATTTGTAAGTGACGCGGGGTGCTGACGGGGTTCGGCCCGAGA5760               GGTGACGGAGCGCCTCACGTCAGTATGATGTCCGATCCGCGTCAGCCCCGACGTGGTTGT5820               GGTCACCGAAACCCACGTTTATATGGACGTTGAGAGCAGCGCCTGACCACATGATTCATC5880               ATACCATTTCTCGGAATCGGGCCCATGCCGGGAAAGCACATTCCTTTTCAGTAAACAACA5940               ATGACATCATAACAAATCATTTTATTCGCGAGGTGGATAATAACCGCATATCAGGAGGAG6000               GGATCGGGTGATGACGCAGGCCCCGCAGAACAGTCCGAAATAAATTTTTAGTATTGCCCC6060               ATAGTCGCCTAGATACCAGAGGTACGTTAAGTTCATCAAAACGCCCATCGGCGTCCCGGA6120               ATCGTATACCGGGCACACGAAGCGTTCATAACAATCCCGGGAGGCGAGTGTTAGGGTAGC6180               AGAGTAGTTTCGGGGTCGGTTTCCTTCCGGCGACGACAGTTCCGTGGGCAGCAGAATGTA6240               CAGCGCCTCGGTAGCTGTCGCGGTGCCTTCCACGAGGATGGGCTGCCGGTGCCTTTCGTG6300               ATTTTCCCCGTCGTGTAGCCAAGCCGAGGCCCGCAAAGTCTTAGGCGAGGGGAATTGTCC6360               ATAGAGTTTCACCGCACCCTTCAGTACATGGTTCTGAATAACACAGCCGCACGTGAAGTA6420               GGTAGGTTCTCTCGTCTCCTCCGTGGCTGCCGCCACCACTCCCAGCCACCACAACAGGCA6480               GATCGCCAGAGGGTTCCGGAGGCTTCCCCGGCGTAGCATGGTTTTGGGTTAAAGCAAAAA6540               GTCTGGTGAGTCGTTTCCGAGCGACTCGAGATGCACTCCGCTTCAGTCTATATATCACCA6600               CTGGTCCGAAAACATCCAGGGAAAATGTCGGTGCAGCCAACCTTTCACATACAGCCCCCA6660               AAACACTTGAATCACTGCCACCATCATCAGCGTATACTGCGCCGACTTAATCGTGAGCGC6720               GTAGTACGCCATTAGACGGCGATCTTCGAACAATAGTCGTTCGATGTCCTCTAACGAGCT6780               CCACAGGGGAACCCAAGGCACGAGGCACCGGGGTTCGCACTCTACATAATAAGTTTGGCA6840               TTGGTGGCAGGGGGAAAAGTAGAACAACACGAGTTTTGTGCGTTGGGGAACACGATAGTC6900               CCGGAGCCAGTAGCGTTTTGCGACGAGGCTTTCGGAGACGTCCTCCACCGGCGTCGGCAC6960               TCGATCCGCGTAGCCCTCCAGCGTCTGGTAGTACACCCGGGGTGTCGGCGTGGGCACGGA7020               CAGGTTCCCGCGCAGGGTCCACAGAGCCTCCAGTCGACCGCCCGATCGGAGCACGCAGCG7080               CGCCTCGGAATACTCTACTCGGTACTCCGAAACATCGGACAGAGGCGGTAACGGCTCCGT7140               CTCCACCAAGGGCGGAGGTTCATCGAAAAGAGTCAAGGATAATTCAGGCATACTACCCGC7200               GACCGGGGCCCAGAGGGCTAGAATAAGCATTACAAGGTTCAT7242                                 (2) INFORMATION FOR SEQ ID NO:4:                                               (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 18994 base pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4:                                        AAGCTTTATTATGAGACATCATACACATAGTATAGGCGAGGTGATGGGGCGGGGAAAGAG60                 TTGGAACCGAAAGACAAAAAAAAAAGCCTAGTCGTACTCGGGATCTCTGAGCGAGACGGG120                TTGCATGGCAACTTTCATTAGTTTGGGAATCTGCCAGCTGGTGCTGTTCGAAGGTTCTTC180                CATTTCCGAGGCGGTCAGTTCATCGTACACCGAAACGTAGTACCTGATGGGGTCCTCCTC240                ATTGTCCGAGAGGTGAGATTCGATGGTCAAAGGCGAGCCTCTCCCATAATTGGGATTCAC300                GAACGACGTGTCCAAGTTGCCATCCTTTCTGAAATAGATGACGTTCTCAGGATCATGTTT360                CATGCGCTCGCGGGCCGCGGACGCCTCCTCCTCCTCGTCCCAGTCCCGAGTTTCCAACCG420                CTGATAAGGGCTCGAGGAACAAAATCCGGCGGGGATCTGAGAACCTCGTCGGGAACCGCT480                GCCAAACGGGCTGCTGCCGCCACTGTCGTCCGTGTCGTCCAACAGGTTGACGGCCTCTTC540                GTCGGCGAAACGAAAGCGGCCCGGGTGCTTGCAACACGAGGAGTAAACTACCGCGATCAG600                TACCGCTATGAAGCTGAAAATGGAGGTGCCTGTCACGATGTAGAAGAGGATAGCCAGCAC660                TTTCATGATTTCGTCATTGCGCGCGTCGTGAACGGAAGATTCGCGGGCAGTGGTCATGTT720                GGTTTCGGTTGTAGGTTCGCTACTCGTGGTGCTCTCGACGGTATTTCTGCTGCTGGTGCT780                AGTAGGGACGTTTGTGCTGCTGGTCATATTTGTAGCGTCGCTGAAGTCGATGTGAAGCAG840                CAACCCGAACGCGACCAGGACCAGGAATGTTGCGCGAAGGAGACCCCGCGGGGCCGGCAT900                TCTTGAGACGTGGCGACGTGGATTTCTTGTTATGTCCGCGAACGACGTGTAACGAGGACG960                TGGTTTCCGCAAGCCTCTACCGACGCCGCGACACCAGGTAGGTTATCAAAACGCGAGCCC1020               ATATCGCCGCCATCATTGTAATCAGCAATGTGTTGAGGTACTGCACGATGAATCTGTCTA1080               GTGACACCAGCCAACCCTCTGCTTTTGCGGGCAAGCGCGCTTTCGGTGACAGGGTGTATC1140               GTACGTAGCCGCGGGTCAGGCGCGCGTTGTAGCGGTACACGCAGAAATCTATCCACAGGC1200               CAACGCCCGGCTGTAGCTTCGGATGGTGGATAATAGCGCGGTGACGTACGCCGCGTGGCT1260               TTAGAATCTCCACCTGTAAGGCCATCTCCTCCAGGTAGTGGGTCTGACTGCGACGCAGCG1320               TCCAGTTCATGTAAAAGTCGGTCTCGCCGTGTCCGGCCACGAAGAGGCTGCTTACTAATC1380               CAGTCTACATTGTGCCATTTCTCAGTCTGATTGCATTTTTTAGAGTTATGTTGCCACCAA1440               CGTATCCTGTTACGTTGATTACCTCGTAACTGCGGTCGCATCTTTTATGGACTGTATAAT1500               TGAAACCATCACAAGTAACGGTCGTGGTGGTGTTGGTACATGTGGTAGTCTCAACGTTTG1560               TATTTGTCGTTGTGGATATCTGTGTGGTTGTTTTCGACGGTTTTGTAGAAACGGTGGTTG1620               CTGGTGCAGTTGCAGTAGAGCAATTTATAGATTCTGAAGTGCTTTTATTGCTGATAACTG1680               TTGTACTGTATGTTGATGTGGCTGTCTCAGTACTAGTGGAATAGTTAACGGTAGTACTAC1740               AGGGACATTGACAGGAACAGGTTTGATTGCAGCTTTCTGATAACGCGGATATTAGTATCG1800               TCCACATAACCGTAAATCGCCAGTCCATTGCAATATTAGTTCTCGCTCAATGGGCATTAA1860               TATTCCTTTGAACGCTGAGCCTTACAGAATGTTTTAGTTTATTGTTCAGCTTCATAAGAT1920               GTCTGCCCGGAAACGTAGCTCAATCTTCATGTTCTGTGTGATATCGAACAATGAATTCTG1980               ATTCACTGACGGTGTCTTGCAACATATGGTACTTTTTGTTAAAGGCTCGTCGTGCAAAAA2040               ACAGAACTATGCAGGCCATACAAACCAACACGATGGTCCATACGGTGCGGCTTCTTTGCG2100               AGCTATGATAGAGATTACGTTTGTGGTGATGTGTATTGTTAGTATGTTGACTTCCTTTCT2160               CTCTATCTTCATTTTCGATATCGGTGTTGTATCTAGGGCAAACGAAAGTAGCATTAATAG2220               CTTCAGTATGATTTTTTGGTGTTACTAATAGGTAGAAATTTTCATCTTCGTGATGTCCTG2280               TGAAGTAATTTTCTTTAAAACAACGTCTGCTGTACCTGCCGGAATTGGTGATATTTAGAT2340               CGTACAGATGTAGTTCTGTGTTGTTGCACGAACGACATAAGTCATGGTACAGTGAAGGTC2400               TTTCATGTTGAGAATGACATACAGTATGAGAGGTAAGGATGCGTAACCAATACCAAGATT2460               GGGTATGTGCGTTCTTACGATGACCTAGATGATGTCCGTGTGTGGATCGATTGTAATGTC2520               GTATCCAGGCGACTGAAAGACAATCCCACGTAGAATTACCTTTTATGGTGACATTACTCC2580               CTTCTATTCCTGTTGTATTAGTTTCTTTGAAACGTATGATTGTTGTCTCTGTGTGACAAG2640               CGTTGGAAGAGTTAGTACGGTTGTACGTGGTGTACGTTGTGGCGCTGCAATTTGTAAGCC2700               ATGGCGTGCTTATAAGTGCAGTATTAGTGGATACGTTGTGCGAAGTTTCATCTGACGTGA2760               TAGTTACGGTGATTGTTGTGTTATAAGATGATGTAGCGTTTGCTGTTACGTTGGTAAAAG2820               ATAATATAGTGTTGGTATTTGTTGAAATCAATTCTGTAGTGGCAGCCGTATTGGATATAT2880               TAGCATATGATGTATTGAATGTAGAATATACGGTTGTGAAAGTACTCAAGTCGGAGGTAA2940               CGTTGGTGATGTTGCCAATGGTTGACGCTTGTGAGGTGACAGATGTGTGTGGCGTCGTTG3000               ATGTGTTGTTATTCGGAGTAGAAAATACGCTGGTCACAAAGGTGGTAGAAGCAGTGTTGG3060               GTGATGTGATGGATGCAGTATTGGTAGTAGTACTGTTGCATGTAACTCTATGCAGAATAT3120               AGAATATTATGATTGTATACGCCGTATGCCTGTACGTGAGATGGTGAGGTCTTCGGCAGG3180               CGACACGCATCTTTTACTGTAAATCCCCGTCCACCGTCAACAACAAAGGTTCCGTATCTA3240               GGTCCGTCCGCAGATGTTCAGCGTCCTGTTCCCCGATTCGTTGCGATCGCAGGAAGCAGA3300               TGACCAGCGCGCCAACAAAGATCATCATTCCCGAAACCCAGGCGCAATGGAGTGAGAGGC3360               CGGACCACTGGCGTTTTAAATCCGAGATAATTGCCCGGTCTGCCTCTTGGGAATCCGTAA3420               CCACAACTCTCCCTGGTCCCGGATAAAAGCATCGACGCGTTTCCAAGGCTCGGCAGAAGC3480               TACGTGGGTGGATGATGAGGTAGAAAGCCTCGACATCGCCGGTATACTGATCCTGCAGGA3540               GGTAGACTCCCGTATCTTTAACCGTGAGATTGTACAGCGTCAGATTTTGGCGCGTGCACG3600               CGAACGCCGCACCGCCCTGACGCGTGGTTTCTTTATAGGCGTCTGTAATGATACAAAGTG3660               GCGGCATACGACGCATGTATCTGCTGTAGATATCATAACGCTGCCAGACTACGCTGTGAT3720               GGCTAGTGTTAAGCCTGGTAACCAGCGTGCGTGTACGGTCCTCGCAGGTGGCACGGTAGT3780               TGGCGAGCTTTAGGGGTTTTTTGGTTGGTTCGACGGCGTTCGATGAACTTCCCTGAGTTG3840               TGAACAAAAACAGCGACGTGACTATGACAAGCGTGAGGGGGGTGCTGTAGGTCTGCATGG3900               TGCAAAACACGTTCTCGCCTTCCTTATCAGACGTTGTCGTCCTCGTCCTCTTCGTCGTCT3960               GTGCCCGTCGGTTCGATCAACGGGGAGTTATCTTTCTGTCTGGAGGGTCGGTATGGAATC4020               CGTTCGTAGATGTTCTGCTTTTTAGCCGCGTGTTGTTCCAGCTTTTTGCGTGTCAGGCTC4080               CGATAGGCCAGACATTGATCTACCTCGGTGCCCGTGTTGTTTTTCTCCTCCTCGCGCGCG4140               TAAATTACAAAGAAGACCACCAGCAGGACTATCAGCGTAGCCACGAACGAGCCCGCGCCC4200               CAGGCCGAGTATGCGCCTAGCATGGTAATGGGTTCTGTGATCCGGCATTTGCACATCGCG4260               TGGCACTTGCTGCCATTGCCGGTATTAGATGATGTGTTATTCGGACTGCACTTGCACGTC4320               AAATGGGTATTTTCTGATTTCACGAGACAGTTGGTGGCGACTTTGGTTTCGGCGCAGACG4380               GCCACATAGCTTACCAAGCTGAGTGCCAGAAAGCACACCGCGTGCATTACACGCGGATAC4440               ATATTAAAACACCGTGTTCCACAAGCACCGCACACGTCAATCCTCCCCGCACGGTCTTCA4500               GCCCGCCCATGACATGATCTCCCTCACGTTACCCTTCAACACCCTGTAGTACTCTGTCTC4560               GGCTTCCGGTCCCCATGTCCTAATTATAACAAAACACCGTGACACTGTCCATCTCCCTGT4620               CTTTTTGCGCCGCCGGTCCCCCCCAAATCATGTCTCTAGATGCCGCCGGCCACCAACCGG4680               AGGCACGGCGGCTATTGGATTCGGCATTGGTGCGCCGCGTCTTGGCCTGCATGATCATCG4740               TCATCATGATTGCCATTAGCATCTGGATCCTGACCTACGTGCTGTTTCTCTAATAAGAAC4800               CCCGGCCCCTGACGGTAATTTTCCTTTCTTCTCCGTTTCTCCTCAGCTGCCGTACGTGAT4860               GCCTCACGGCCATCTCCGACAGGCCCTCTCCCCGACCTCCTGGACATGTGAGGGCTTGTT4920               GCTCCTCCTGGGATTGCTGGTGCTCTTCTTTCACCACCACAACCAGTCGGCCGTGGAGAG4980               GCGTCGCCGCGTCTCGTTCGTCGAGGCCGATCGACTGCCGCATGAGAGCGGGTGGTATTC5040               TTCCGATGACGACGGAGACCGGGACGGTGATGAGGAAACTGGAGAGAGCCACAACAGAAA5100               CAGCGTGGGACTGTCCGCTGTTTTTAGCTGACTGGCGTGCGACCTGTAAACCGTTACTCG5160               GGTCTCAAGATGGTTTGGAAGTTGTGACTCATCTTCCTGTGGGTGATACCCAACCGGACG5220               CGAGTGTTCCATAAAAGCCGGGCGCTCCGGCGAGACCATGCCATCCTCGCCTTCGGACGC5280               CCCGCTCCTCTTCTCTCTCCTCTCCTCCCCGCTGCCGCGGCCATTGCCGCCGCCGCCCAT5340               ACCATCGGCATGTCGGCCGACAAATCGCAGCTGTCTTCGCCGCCGCAGCTGTAGCAGTTA5400               ACGTCGCCGGCCTCCAGGAGGAGATGGCGCTGTGCGTCGTCTCTTCGTCCCGTCTCCCTC5460               TGTGGTCGTGGGTGGTGCGAGAGTACACGATGGGTGGCTCTCGTCTCGGGGGACCACAGG5520               GGGAGGGGGGTAATTTATTATTCGTATTACTGTAATTTTGTATCGCTTAATTTGTTTAGA5580               GCCGCACGCTTGACAACGCCTTGTATAGCCTTATTTATCCCGATGACTTTTTTCTCCGTA5640               CAAGAAATGGACGTCACTTGAGCAGACACAGTTTCATCGACCACGACAGTCTCATGATCT5700               GACTACCTCTGACCCGCCAACGAGAAAACCGAAAAGTAAAAGATGACCGCGCCCTCGGAG5760               TCCTTTTTTCCTTTTCAATCATGAAAGCAAGAGGCAGCCGAGAGAATGCCAGTAAGAGAC5820               GACCATCGCAGACACAGTACGATACTCATCTTAGAACGAACCAGCGAATAACCATCACAC5880               GTACAGCAGAATCTCATGAACTAGTCAACCAACGTCATAAAATCTTCACACAATCGTTTT5940               TGCGAACTTTTAGGAACCAGCAAGTCAACAAAAGACTAACAAAGAAAAACCATCTTGGAA6000               TTAAAAAAAGTAGCATCGTTACCTTATGAACCAGCAGCATTCAGTATATACACCAGATAT6060               AATATATTTATTAATGTATCCTCTCTTTCTCCTGATGTAATTTTGTTTTTGTAAATTCAA6120               TTGTTGAAAGTCTCTCCCTGGGGGAATTGCATATCTTATTGATGAAGAAGAAATCCCTGC6180               CATATGTGTTGTCAAACTATCATTATTTCTCTATATGGGTATTTTTTTTCTAAGAAGCAA6240               AAGACTAGCAGCAGCCAAAATAAACCTGATGAAATCTTTAACTGAACTCCCAGTGGTCTG6300               TGTGTATATTTCTGTTGGTGGTCGGTTGTCTGAACCCGGGTGGGTTGTTCGGAAACGGCG6360               GGACGGGGAAACGGATGGAAACAGCGTCGCTATATACGTGACTTTTGATCTAAACGGACG6420               TCGCTAGGCTGACAGTTTACGAATTGCTAAACAAGATAGGAACAAAACAAGCGGGGCTTT6480               GCCTGGTAGGATTTCCTGTGGAAACAATAACCGGATGTGATTGTGGCTGGTACATAAGCT6540               GGTTCTGGCTGCAAGCGCTTTTCACTGCATTAGGTTTGGCGTTTGCTTTTGCCTGGGAAC6600               GCTATGGCTATAACGGGAAAGAACCGGTTTGGCAACATTCCATTGTGGGGGGGGGGTACT6660               TATAGCGTGCCTAGCTATGACGTTGATATATGTGGATGCGGATAATACTCGTAATGAGCT6720               AAAAGCGACGACTGGTAGTAATTTTACCATTACGCATAGGAAAGATCCGTTGACAACTAA6780               GTGGAAAACCGTTTTTGGTAACAATGGTGATCAGTGGTTGTGCAACGTTACGGGTATAGG6840               TAATGCTACTGTGAATAGTAACGCAACTATTTGTGTGTCGAGCTGTGGTCATAATACGTT6900               GGATTTATGTAATTTAAAGTCGGGAGATTCTGGCTTCTTCGATCTGTCTCGTTGGTTCGG6960               TGAAAACATGGATGAATACAGTGGTGATGTGTGGCACTTGGAAGTCAGCTAAATGTTGTA7020               TCGCTTAGTGAATTGGTGTTCTTACAGTTTTCATGTAATAAACTACGTGTAATTCGTTAA7080               ATTTGTGTGTTTTTTTGTTAGTATTCTGCGTAACGGTGGAATAAAATTGCGTTGACCTAG7140               TTAGATTTCCTGTGTAGAACAATGACCGGACGTGCTTGGACTGGTACATACGCAGGGGCT7200               GGACGTGGTTACCGGTCACTGGACTCGGTTTCGCTGTAGCTGTGGTTCAACCTGAACATG7260               GCTCCCAGAGCTGCTAGGAACCGGTCCAGTCACATTTTTTGGTGGGTGGGGGGTACTAAA7320               AAAGTGTTTAATATTTGGGTTTAATGATAAAATCCAGGTTATGGATATGAGGAAACTGAA7380               TACCTCGCAGGGTCGAAATCTTACCACAGTTGATGATAGAAGACGGTTTTCCATCGGGTG7440               GGAAACATGGGATAACGGTGGTGACTAATAATGGTACAACGGTCGTCAATACAACAGCCT7500               GTGTTTCAAGTTGTTCGCATACGTCGCTTGTGCTTTGCAATATGACGCAGCAGACTGATT7560               CGTTGTACGGAGTGGGTCATCGGTTGAATGACGAAGAAGATGGTGAACTGTGGAGAGTTT7620               CGGTTTCTTAATAATCCCATACGACATGTGTTCATTTATATCTGAATTTTAGGATGATGA7680               CTATAGTATAACTCTGGGGAACAAATATCATACGTTAATCACTTTAAGTTACGCCGTTAG7740               GAAAAGAAAATCAGTCCGAATGAAGCATAGTCAGCCGAATGATACAGCAATAGCTTGTTT7800               ACAACGTGTTCTTTTTTACATTATGAACGTGCCTTGCTTTTTATACACACATGGAGACAG7860               AGGTCCCTCAGCCCTTGTCACGACAACTCCCTTTTTCTAAACCGTATGTGCTCCAAACCG7920               TATCTCCTCATCGTCACGTGAAATACCATGGGACCCCTTTTCGTCACACACGTCTTTCCG7980               CTTACCCAACGCGTCAGCCCGCGCTCGGCAGAGCTACCATATAAAAACGCAGGGGTTTAG8040               CAGCTTCCCCAGATCGCTGCTGCCCCGGCGTTCTCCAGAAGCCCCGGCGGGCGAATCGGC8100               CGGCTGGTCGGTCGGCGCTCGGACGGATGGGGAGAACGGCGGTGACTTAGCCGCCCGTGG8160               CCGGGAGAAGACGGAGGAGCCGAGATGACAACAGCAGTCGTGGAAGGGTCGCCAAGCCCC8220               GGTCCTTCTCTTCTGTCTGGTCGAATCTTGTTTTCTTTTTTCAACCGCTCTTTTTGTCAC8280               CTTTTTATGTGAGTTTCTCTTCCGCGTCTCCCGGCCGTACCATCCACCCATGCAGCATGC8340               ACGCGTGTATGTATGCATCGCCTCTCCTCCGTCCCGACTACCATCAGCAGTACCACTGCC8400               GCCACCCCCAGCGCCACCACCGCTGCCGTCGCCACCGCGTTATCCGTTCCTCGTAGGCTG8460               GTCCTGGGGAACGGGTCGGCGGCCGGTCGGCTTCTGTTTTATTATTTTTTTTTATTTTTT8520               ATCTTCTCCTTTCCTTAATCTCGGATTATCATTTCCCTCTCCTACCTACCACGAATCGCA8580               GATGATAAACAAGAGGGTAAAAAGAAAAAAGCTACAGACATTTGGGTACCTCAGCTTTCC8640               GATAACTCGAAGAATTCAAAGTCGACGATTCCCAACAAGAGAAAACAGAACAAAAACAAG8700               GTCATTTTTATTTATCCTCATCGTCAACAACAACTACCGACAACAACGAAACACCACCAA8760               GAATGTCAATCCGCAAGGGTGTTCCTGCCCCCTCGACGCGCCTGTCGCGATCCTCATGGC8820               GAGGACCGCGATCTCCGTATAGGTAGATGAAATTATCCCGTGTCCGGTCCTGATTCCCCG8880               CATGCCCTGCACATCCTGACGCGTCGGTCAGCAGCCAAACAATCATAGGAAATGAACCAG8940               AAGAACAAAAAGATCATCTCTCTCGGTGTATAGCAACACCAACAACAACCGCATCGCAAC9000               ATCTTCATCCGCAAGACGGAAAGAAAACAACAATAATGAGAATGAAATCACCACAACCAA9060               GCCAGATTTCACGTCCATGAGTTTTTATTATATTATTATCAAAACGAAAAACAGAAAAAC9120               TGTCATAGATAAATATAAAAAAAAATAGAAACCACAAACGACTACTAGTACTCCAATCTT9180               AGATGTATATGCTCCTAGATAAGATTTAGTATTACCATAATCATCGAAGAATGAAAGACG9240               ACGATGATTCCTTACCGCTCCTGCCACCCGGTCTGTATGTAGAGAGAGAAGAGAGAAAAC9300               GGTGAATCCAAGATCCCCGGGTCGGCGTCGGCATGCCGCTGATCGCAGTGGCCCCACCTC9360               GGCATGCCGGCGCCGGGCGAGGAATTGCTCATGAAAAAAAGTATCTTTCTGTAAAAAAAG9420               AAAACAATACATGATTAACCGAAAAGAAACCAACAAAAAGAACCCGAGATCAGTCGATTT9480               CGATCACTACGATAAACACATGGAAGATTTCTTGAAAAAAGAAAAGAGAAAGAGACCACC9540               TTCCCGGCGGCGGACACGCTCCTCTCCGTCGCCGTTCTGCACCATGATTCGATCAATAAC9600               AACATCATCATCGGAGACCATCTTTTAATCAATCAGCGTTGCAGTAGTCGACTCCCTGGA9660               CACGAAGGAGTCATCCATTTTTATCCTCGCACTTCTTCGCTCTCAAAGCCGCCTTTAAAG9720               TTGAAATGAAAGGATGGAAACATGGAATACAGTTTTAATTGCACGTATCACCATTTTACT9780               ACAAAAAGAAAAAAAAACAACTTACACATAGTATTACCTTAGGTTTACGGATAAGTAGAG9840               TGTAGGCGTTTTTGAAACAGTTCAGCCAATGCAATCTTGTCTCGGCATAATCACTCTTTC9900               TGCATATAATAGTAGTAGTAGATTTATTCACATCAACACAGCGAAAAACTCCAGCATCAA9960               AGTACACCTAGAGACAGCCCTTAAAATATAGTTTGCAGCTTTTAGATGTACTTACACCAA10020              AGAAGATTACCGTCCTTACGAGAAAACAGATACTCGGATATAGGAATCAAGACAGCTCTG10080              CACTGAAAACACACTCTCCTGTCACGACACCGCGCCACACCAGAGGCGTACGCGTGACTT10140              CATCGCAACGATCCATCGTGATGTCCCTCGCAGAACCTAAAAAGACCAAAAAAAAATCTT10200              GGACCACAGTTGTCGATACTTGAAGACAATATTCTCGTGAGAACTTTGAGATTCGCACTT10260              GAAACCTCTTAGGATCCACAAAAACAACAACCTCTGTATGGAAAATGCGCTATTTTATCT10320              CAGCTTTTCTCCCAAACCTCGGTTTCTTCCTATTCTTATGTTTTCCCTAGTATATTTGCC10380              TCCTTATAAGAAAAGAAGCACAAGCTCGGTCGCACGGATTATTCCTTCTGCTAATCTATT10440              ATTTTGTTCCTTTTTTTTTTCTTTGCCTTCACCCTCTTCACTCCCTGTAGCAACACAGAG10500              TAGTAGACACAATAAATGAGAAGTTTGCATGCATTTGTCGTGTCCGTGGTTTGTTATGGC10560              GTGTGGAGTGCTCGGGATGGGTGGACGTGGGGACGGATTCTTGAGGCTACAAAGATACGC10620              GGAGACGTCGTGGCGAGGGGATGGGTTTATTGGATATCGGTGAAGCAGCGTGGCGGCGAA10680              AGACGCGATCCCTGGGCTGGTAGATCCCCCTACCCCGTCTACCAGGGACGTTTATCCTTT10740              GGACACGTAAATGTCTCGGCCGGCATCCACGCGCCACGTTCACCGCGTTGTGCCCAGCGC10800              CATGTGCGGGTCGTTTCGGCGTGAAGTTGGACGGCGTAGTTTCGGGGATTGTGAACCGTG10860              GCTGAGGGTGTAGATGGGACAGGAAAAAGCGTGTGATCTGACCGAGGCGAAGCATGTGGG10920              TGGTGCGATGCGGTGGATGTGGCGGGGTGCGGCGGTTTCCGACGTGGAGATGTGGAGATG10980              GGGGTGATCCGGATGCGTGGCAAGAGGCCTCGAGCTTGGGCTTCTCCCGCGGATGGACGT11040              TCTAACTGTACACGGCGGCCGTGGCCTCCGAGTAAAAAAACCAGGTGCTGACGCCAGACA11100              GAGACGCCGTCCTCGGAATCGTGTGCGCGAAAGCCTGTGCCGCGGCAGCGTACGACGTTC11160              CAGTCAGCGAGGCCGTCGCGTTGGCGCGCCAACAGTAAGGTGACGACAGGTTGGCGGCCC11220              ATGGTTCCGAAGCGTCCCCACATGCACCAGCAGTCGGCGTCAAAGTCGCTTGCGCTGTCG11280              GCCCAGTCGCCACCGCCGCGGCGGATTTCCGCGCGGGGGACGGGGTAGCCGAGTGCTGCG11340              CCCTCGCCAATGTTGTGAAGTGGATGCGTGAGTTGATGTTGATTCTCTGTGGGAAAATGA11400              GCGCTGTCCTGTGGGTTGGTGTTGGGGTATGCGAGTAGTAGGGGTTGTGTTTGATCGTAG11460              AGGTGTTGGCGGGCCTGTGCGCAAGCAGCGTAGTCTGCGGCGTCGAGCTCCATCTGTGTG11520              CGGTGTTCTTCGTCGGCGTGTTTGTCCGAGGTTTGGACATGCGGTTGTGTGTTGCTGTGG11580              TGTAAGGGTAACGTGTGTTGGGCGTCTGGGTGAAGCGGCGTGGTGTGGGTGCTGTTTGTG11640              TCTGTGGCTGGCATGATTGTGCGGCATGTGTGTGTTGTAGTGGGTGGAGGTTAAATAGGT11700              GAGGTGGGTTCCCTGGTCCGCGCCGCAAACTGTCCCCGTCCCCAACGTAACCTCCCCTAC11760              GCGGCGCGAACAGCCCCGGCCCCAGCGCAACCCCCGTCCCCGGCCCCAACACCGTCCCGC11820              ACACCCCCCGTCTCCGCAACACCCCGGCATCGCCGGCGGCCAGAACGCTCGAAAACCCCC11880              GACAAGCGCAGCGCCGAAACGACACAGGCAAGGACCGTGGAACGCACCGGCAGCGCGCCG11940              AAACACCGTCCCGAAGCCCGGTGCCGACAACAAATACCGTGGGACGACACGCACCGGCAG12000              TGCGCAGGCAGCGTCGGACACAACACGCTTACGGCCCTCAACACTCCCTCGAGGACCCAC12060              CACGCGGCCCCGCACCGGCGGTGTTTTGGGTGTGTCGGGGCGCGGCCGGGTGGGTGTGTG12120              CCGGGTGTGTCGCGGGCGTGTGTTGGGTGTGTCGGGGGTGTGTTGGCAGGGTGTGTCAGG12180              GTGTGTCGCGGGCGTGTGCCGGGTGTGTCGTGCCGGGTGTGTCGCGGGCGTGTGGCGGGT12240              GTGCCGGCGGGGTGTGGTGGCGGGGTGTGTCGGCGGTGTGCGCGGCCTCGGGGTGTGCGG12300              CTTCGCAGGAACGAGTGTGTGGCCTCGCGGCCGTTATTTCCCCCGCGGTCCCCAGGGCCG12360              TCGTCCCTCGCCCCCGGGCGTTGCTTTTCGTGTGTCCCCAGGGACCCATGCTGCCGTCCC12420              CCGGGAACTTCCTCTTTTCCCCGGGGAATCACACAGACACAGACACGCGTCTTCTTTTCG12480              CCGTGCGCGCCGCACGTCGCTTTTATTCGCCGTCGCCGTCCTCCGCACCACACGCAACTA12540              GTCGCCGTCCACACACGCAACTCCAAGTTTCACCCCCCCGCTAAAAACACCCCCCCGCCC12600              CTCGAGGACCCACCACGCGGCCCGGAATGGATGTCGGGCGTCCACCTAGATGGGTGCGCG12660              CCCGGGAGGCGGCTGTGCGCTCCAGTGGTACGCGCCTGCCGCGCGTCTTCCTTCGGGTAG12720              CTGCCTTTCCCAGTCCACGGCCTTCCAGACTGCGTGGCGCCAAGGCGGCGCCAGCACGCG12780              CCGTGCACGTCGCTGCCTATAAAAGCCAGCTGCGTGTCGCCCGCGGCACACGGGCGACGA12840              AGGCGTCCGCGTGTCTAAACCGCGTGCTCGCTGACGCGGGTTTGCTTCCTATATAGTGGA12900              CGTCGGAGGTGTCCGGCGCCCATGGCCCAGCGCAACGGCATGTCGCCGCGCCCCCCGCCC12960              CTTGGTCGCGGCCGCGGGGCCGGAGGGCCTTCGGGGGTTGGTTCCTCTCCTCCTTCTTCT13020              TGTGTGCCGATGGGAGCGCCGTCAACAGCGGGCACTGGTGCGAGTGCTGCGGCTACGACG13080              ACGCCGGGCCACGGCGTCCACCGGGTAGAACCCCGCGGGCCGCCGGGCGCCCCTCCGAGT13140              AGCGGCAACAATAGCAACTTTTGGCACGGCCCGGAGCGCCTGTTGCTGTCTCAGATTCCG13200              GTGGAGCGCCAGGCGCTGACGGAGCTGGAATACCAGGCCATGGGCGCCGTGTGGCGCGCG13260              GCGTTTTTGGCCAACAGCACGGGCCGCGCCATGCGCAAGTGGTCGCAGCGCGACGCGGGC13320              ACGCTGCTGCCGCTCGGACGGCCGTACGGATTCTACGCGCGGGTGACGCCGCGCAGCCAG13380              ATGAACGGCGTGGGCGCGACGGACCTGCGTCAACTGTCGCCGCGGGACGCGTGGATCGTA13440              CTGGTGGCTACCGTGGTGCACGAGGTGGACCCCGCAGCCGACCCGACGGTGGGCGACAAG13500              GCCGGCCATCCCGAGGGTCTGTGCGCGCAGGACGGACTGTACCTGGCGCTGGGCGCCGGG13560              TTCCGCGTGTTCGTGTACGACCTGGCAAACAACACGCTGATCCTAGCGGCGCGCGACGCG13620              GACGAGTGGTTTCGGCACGGCGCGGGCGAGGTGGTGCGGCTGTACCGCTGCAACCGGCTG13680              GGCGTGGGCACCCCGCGCGCGACGCTGCTGCCTCAGCCGGCGCTCCGACAGACGTTGCTG13740              CGCGCCGAGGAGGCGACGGCGCTCGGACGGGAGCTGCGCCGGCGGTGGGCCGGCACGACG13800              GTGGCGCTGCAGACGCCGGGCAGGCGACTGCAGCCGATGGTACTGCTGGGCGCGTGGCAG13860              GAGCTGGCGCAGTACGAGCCGTTCGCGTCGGCGCCGCACCCCGCGTCGCTGCTGACGGCC13920              GTGCGTCGGCACCTGAACCAGCGTCTGTGCTGCGGCTGGCTGGCGCTGGGCGCGGTGCTG13980              CCCGCGCGGTGGCTGGGCTGCGCGGCGGGGCCGGCGACGGGGACGGCGGCGGGGACGACG14040              TCGCCGCCAGCGGCGAGCGGCACGGAGACGGAGGCCGCCGGCGGGGACGCGCCGTGCGCG14100              ATAGCGGGAGCCGTGGGGTCCGCTGTACCTGTGCCTCCGCAGCCGTACGGCGCCGCCGGC14160              GGGGGCGCGATTTGCGTGCCTAACGCGGACGCGCACGCGGTGGTCGGGGCGGACGCGGCA14220              GCAGCAGCGGCGCCGACGGTGATGGTGGGTTCGACAGCGATGGCGGGTCCGGCGGCGTCG14280              GGGACCGTGCCGCGCGCCATGCTGGTGGTGCTGCTGGACGAGCTGGGCGCCGTGTTCGGG14340              TACTGCCCGCTGGACGGGCACGTGTACCCGCTGGCGGCGGAGCTGTCGCACTTTCTGCGC14400              GCGGGCGTGCTGGGCGCGCTGGCGCTGGGACGCGAGTCGGCGCCCGCCGCCGAGGCCGCG14460              CGGCGGCTGCTGCCCGAGCTGGACCGCGAGCAGTGGGAGCGGCCGCGCTGGGACGCGCTG14520              CACCTGCACCCGCGCGCCGCGCTGTGGGCGCGCGAGCCGCACGGGCAGTGGGAGTTCATG14580              TTTCGCGAACAACGCGGTGACCCCATAAATGATCCCCTCGCATTTCGTCTTTCGGACGCT14640              CGAACTCTCGGTCTCGACCTCACCACCGTCATGACAGAGCGTCAAAGTCAATTGCCCGAA14700              AAGTATATCGGTTTCTATCAGATTAGGAAACCTCCTTGGCTCATGGAACAACCTCCACCC14760              CCATCTCGCCAAACCAAACCGGACGCTGCAACGATGCCCCCACCGCTCAGTGCTCAGGCA14820              AGCGTCAGCTACGCGCTCCGATACGATGACGAGTCCTGGCGCCCGCTCAGCACAGTTGAC14880              GACCACAAAGCCTGGTTGGATCTCGACGAATCACATTGGGTCCTCGGGGACAGCCGACCC14940              GACGATATAAAACAACGCAGACTGCTGAAGGCCACTCAACGACGAGGCGCCGAAATCGAC15000              AGACCCATGCCTGTCGTGCCTGAAGAATGTTACGACCAACGCTTCACTACCGAAGGCCAC15060              CAGGTCATCCCGTTGTGCGCGTCCGAACCCGAGGATGACGACGAAGATCCTACCTACGAC15120              GAATTGCCGTCGCGCCCACCCCAGAAACATAAGCCGCCAGACAAACCTCCGCGCTTATGC15180              AAAACGGGCCCCGGCCCACCTCCGCTGCCGCCAAAGCAACGGCACGGTTCCACCGACGGA15240              AAAGTTTCTGCGCCCCGACAGTCGGAGCATCATAAAAGACAGACCCGACCGCCAAGGCCG15300              CCACCGCCCAAATTCGGGGATAGAACCGCGGCCCATCTCTCGCAAAATATGCGGGACATG15360              TACCTCGATATGTGTACATCTTCGGGCCACAGGCCACGGCCGCCAGCACCTCCGCGGCCG15420              AAAAAATGTCAAACACACGCCCCTCACCACGTTCATCATTGAAAGTCTCTCCAGTCCATA15480              TGTTGTCAGGACGTGCTGTCGTTCTCCGCTTGCTGCGAAGCCCGTTCTTCCGAGTCGTGT15540              CGCTGCGTCCAGCGTCGCGCCCAAGATGGGAATTTGGGTCTTTTCACGCGTAGCCTCCTC15600              CACCACGGCTGCTGATCGCCGTCACTAAGGACCGACACGGAGGATGACGAGGAGCTTCTC15660              CCCGACTCCGCGGTCCGCGACCGGCTACGTAGCGCGTGTCCCTGCCAGTCTCCGCAGTTA15720              CACCACACGTCGTGAGCAGCGTGCACCTGCTGCCGCCACTGGGCCTCGGCGTGCTCAGGC15780              CACCCGCCGGAGCCCGGTCTGAGCTCCGACGCAGGATGCGCGTACTCAACGTGCGCCTTC15840              CAGTCCATACAGCAACACCATAGGTCGTGCGAGTCGTCGGCTACCCGCCGCCAGGCCAGT15900              TCCCGCATGGGAAGGCTGGACACGCCGACCGAGAGGTCACCGAGCCCGGACGCCATCTCT15960              TCTTCCTCTCCGTCGCTGTCATTAAGCAGCCAGGTCACCTCCTCCGCTCCGCGTCCGCCG16020              GTCTCGACGGACCGCGCCGCCGTCGGCAACACGGAAAACAGCACGCCAGCCCGAGCCGCT16080              AAGGCCGCATGCCCCTGCCGCCCAACTGAACACGCATACCCCGCTCAACTGCGTTTTGCC16140              ACCCCTGTCAGTGCTCTCGCTCGAGCACCACCCCGCATCTCCCAACCTTTTTCCAATAAA16200              CGAAACCGACATGACACACGTAATGGGTACTCGTGGCTAGATTTATTGAAATAAACCGCG16260              ATCCCGGGCGTCTCAGCACACGAAAAACCGCATCCACATCATAGACAAGTTACAGTCCAC16320              AGTCACATACACGATAAACAATACCAACAGGGTAATGTTTATGGAGTAAAACACTATTGT16380              CCAGGCCACATGCGTGTATGACTTCCGCACCATCCCGTACTGCATGTTCCACATGTACGC16440              GCTAGACGTGTAATCCACTCGCAGTTCGGGGACGCAACGCAGCCAGATCACATCCCCTTG16500              CAGTACCAGACGCAGGGCTAGCGTCTCGAAGATCGGCATCACATCTAAGTTCCGCACGTT16560              CCACTTTAACGACTCCCCGGGAACGAACTCCACGTCGTCGGCGTGTACGTACAGGTTCTC16620              TCCCACGCCGCCATAATCGGCCTTCGGATCGAAGACGAACCGACTCATGTTGCCCACGAT16680              GCTCCCCCGAGCAAACAACTTGCCGTTGTCAATGTAGCACCGGTTGTCCTCGATTTGAAA16740              CCAGGGATGCTTGGCCGTGGACTTCCAGGGCCGGAGCGCGTCTTCCCCGGCTTTAGTGAT16800              TCCATCGGGCAGGCGGATCAAGGGACCCATGGAGGTCCAAAGACCCACCCAGGCTTTCCA16860              GAGATTGTTCATGGTGAAACAGCGTGTGGACTGTACGCTCTTTCCCAATTTATATCCCAG16920              AGTAGTGACGTGAGCCCAGCCACCTCCCAGATTCCTGACGTTTTGGTTGTCTTTCCTGCC16980              AATTCCTCCCGTAAACTTATGATTATCCTAGCCCATTCCCGATAAAAATACACGGAGACA17040              GTAGATAGAGTTACGAATAAACCGGTTTATTTATTCAAGTGTCTCAGGAGATTATTGAAC17100              GAGCGTGGATACCACGCCGTCGTCAGTTCATGGTGGCATTGAGCAGCCATAGCACCAGAG17160              TCCCGGCGCCCGGTATCAGACACGCTGACCTACCGGGCGCCTTCGAGTCCGTACCCCGCG17220              GCCTGGGTGTTAGAGTCCGTACCTTGCAGCCCAGGTAGGTTTCAGGTACCAGCTGGTTCG17280              TACCTGTTAAATAAATCGCAGACGGGCGCTCACCCCTACGGTCAGGAGCACAAGAACAAC17340              CAGAGAGAACAGATATACGAGCAGGGTTCTGAACAGCAGACCCCAATTGTCGTCTCTCAT17400              GCTTCGCTGAAGGTACCAGTTGATGGTCTGAGAGCTATAGTCCATCCTCACCTGAGGAAC17460              ACACGCGGCATATTTCTTGGGGTCTCCCCACCTCGTAGACAACGTGATGTCCACCATATC17520              CACGGTGTGCGTCACCGGGTGCCCACCGATGTTCCACTCGAAATAGGCTCCGCGCTCATC17580              ATGGTGGTACTGCTCACCGGACACCTGCAGTCTGTCCATGTAAGATTGAGAGACGATACC17640              CACGTTCACAAAGTGTTTCTCGGTGAAGTTGCCCGACATCCTCCCCTTGAAGTACAGCAT17700              GCCCATATGGAACCAGCATTGGTTCTCCTCCACTCGAAAGTGGGCCGATCTGATCTCCGA17760              TACCACCACATCCAGGGGCCGGGGCACCGAGTCCGCGAGTCTCAGGAACAAGACGGCCAG17820              GATCGCGAGCACCAACACCGGCTTCATGGCTCCGAAGGTCCGCTGCTCGGCTCCGCTCAC17880              CGCTCCGGTCTGGCTGCAGCAGTGCTTCGCTGAGAAGTAGCGTGTGGACTGAACGGTGTT17940              TTTGAATATATAGCGTTTCTTGGTGACGTTGTTTCCCCTACGTAGTAGGCAACTACGTGC18000              CAAAAGAGGCGTTACGGTACTTTCCGTACTGGGATTTCCAAACCGGGACTTTCCACACGG18060              CGGTTTCAACACCGGGACTTTTCACACGGTGATTTCGGCACCGGGACTTTCCGCACGGCG18120              GTTTCGCCACCGCTGACGTTCTCATCGCCGCCCACGTCAACGGTGGCGACACCGTACTTT18180              CCCATGCGGTTTATAAACGTCAAGAGTCACGTCAGTCGCCCACCCCCATTACACGGCGAT18240              ATCCCGATAGGGCATGAGGGGACCCGGGTGTCGCGACATGTCGACGACAGGTGCGGATTA18300              GTGGTCGTGTCGCGACATGGACGTGCAGGGGGATGTCTGTCGCGATAGAGTTGATGTGAC18360              AGCCCGCTACACCTCTCTGTCGCGACATGCATACACAACGGGCCGGCTTGTCGGCGATTG18420              TCGCGACATATCGTTATCAGTTAGCGACCGGAGTTGTCTATCGCGACATATCGTCGACTA18480              TCGCGACAGAAAAAATACCGTTCGTAGAGAATGCCGTGTTGAAGGAACGCGCTTTTATTG18540              AGACGATAAAACAGCATCAGGAGCCACAACGTCGAATCCCACGTCCAGTCGATTCGTATG18600              TTATGCTGCACAGCAATGCTAGAATAACAACCAGCAGGGTAATCCCGCAACATAAATACA18660              AAGTCACAGCGAAGAATCCGTGTCGTTCTATCAAGCGAAACGCGTTCCAAACGGCCCCGT18720              CACAGACGCAGTTATTCATAAGCGTTAACAACCGGTGGCTAGGATGAATATCCAAATCAC18780              AGGGCAGTAGCCGACGGACTCGTTGACAGGTCAGCCTACCCTCAAGGTTCCTATCGTTCG18840              GACGGGATTTGTGCGTTTTAGGCCTCTTTTTCGCCGCCTGCAAGCATTGGTGCGCAAAGT18900              CCTCACCCAGCTGTTTCCAGCTATCATCTGCATCTGTGCAGTCCCCTGTATCGTTGTAAC18960              AAACGGGTCTGTGCGACTTCGTTCTCGGAACACA18994                                        (2) INFORMATION FOR SEQ ID NO:5:                                               (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 5020 base pairs                                                    (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5:                                        AAGCTTGTTGTCGCGGAGACAGAGAGAGAAGGGTTTTCGGGTCACGCGAAGACCGCTCAC60                 CGGGGGTCGGCAACGCACACATCAACAGAAAACCGAGACGAATCAAGAGATCCATAGTGA120                AGGAGTGATATCGACGTGCTTACGAAACGGCGATTATATATGTTCTCAACAATACCGCCC180                TACGTTGTATGATGTAACGTGTGACGTGAGTCTGATCCAACACTGAACGCTTTCGTCGTG240                TTTTTCATGCAGCTTTTACAGACCATGACAAGCCTGACGAGAGCGTTCATCGGGGCATGA300                AGTACGCATTACACAAACTCCATATATTTGTTACGATAGAATACGGAACGGAGGAGGCTT360                TCGCCACACCTATCCTGAAAGCGTTGCATTCTTTATGATAGGTGTGACGATGTCTTTACC420                ATTCCCACGGCTGCTTTGCGTGATGATGACATTCATCATGTATTTCCATTCACACATACC480                TTTTGTGCATACGGTTTATATATGACCATCCACGCTTATAACGAACCTAACAGTTTATTA540                GCCCTTGACAGGATAGGTCAAAAGATTATATGTAGGTTTTCCGGTAAACCGAATTGTGAT600                ATTTCTCTGCAGGAAATAGAACAGCCTGGTACCTATAAAACGGACAATGCAGTACTGTAG660                CAGCGTAACCAAGTAGGTCCACATGAACACGTACAAAATTATGGTAAGCCATCGTTTTTC720                ATACCACAGCCTGTAGCTGTCGTACATGAATGAGGACGGTCGAGGAACCCAGGGTAGTTG780                TAATTGGGGGCGACATTCGTACTGTCCAGAAGACAATTGCACGGGTTTCAGTGAGATGAG840                TACTTTAGCGATGTCGGCGGGGGCGCTACGTTTCACCGTGACGGTGAGAACTTGACCGTC900                GTTTTGTATTTCATGAGGCACGTTATACAAGCCACTGGTATCATGAAGGATGACCTCTGA960                TGCGATGTGAGGATTAAATTGTCCCTCAAACCGCCAAACGCTGGTCATGTTTCCACCGTC1020               AATTACGCAGCTGACGGTGTGAGATACCACGATGTTGGACTTAGGTTTGGGGGCTAATTG1080               CCTTTTTACAAATTCCCTTCTGTATTGCAGGTCCTGCTGCCACTGCTTTTCCGTGCGGAA1140               AGTCGCCATGTCTTCCACACGTGTGGCGACGATAGACGCCACCAAGGTAGCTACCAGAAG1200               CAGCTGGATCCGCATGGCATTACCGTATGTCAATTAGAAAGTTGAGCGGACACGGTTATC1260               GTTCCTGGCGGATATAAGTATATAAACGCGAGTTAGCCTTTCCCGTCCGTTTTGTACACC1320               CGTTCCCCACACAAATGACGAATACGACCTTTTTTTTTATAAAAATAAACCACGTGTATT1380               ATATAAAAACATTTACATAGAAAAGAGACACACGGATCAACATAAGGACTTTTCACACTT1440               TTGGGGTACACAGGCGTGCCACCGCAGATAGTAAGCGCTGGATACACGGTACACAGTCCT1500               GGCCAGCACGTATCCCAACAGCAGCACCATCGCCATACAGATGGCGATCACGACCCCGAG1560               CTCTAAGTGTCTGTATTCATAGTGTAGTCGCCGCAGGTTATCCACTGAATTCCCGTAACT1620               GAAATAACGTATATGGTACCGAGGCTGGCACCACATGGGTTTGCATTTGGTGCACGGCAC1680               CAAATGCAGAGTGAGATGGTCCAAGTCCGTGGGCACCCACTGGCGCAAACGGAATACGGC1740               TTCGGTGGTCTCCACGAGGCACTCCGGGGCGTGCAGACGGCCCCACTTTCGTCCGCGACG1800               GCCCGACCAGCCGACCCGAGCCACTATCCCTTTCTCGGGATAGAACGTACCCTGTACACG1860               CCACACAGCGTCCAACACGCCGTCCTTGACGACGCAGCTGGCCTGATAGCTGGACACGTT1920               GTTAAGCGGCGGAAAGCGAAACTGACGTGCCGGCGGAGCCACATAGTTCGGTTCACCGTG1980               TTGTCGCGGTTCGTCCTCCCTATAGTAATAGTAGTCGTCGTCCTCATAGGGGTTGCCGGC2040               GTGAGCCAGCGTTACCCAACAGCAGCCCAGGCCGACGAGGAGGCGCAGCCACCGCCTCAT2100               GGCGGCTTCGCCAGTCAATCGTCTTTAGCCTCTTCTTCCCGTGAGGTCCTTCCGGTGGCG2160               CGGTGCCGACCTCGGACCCAGGGACGTATCCACCTCAGGTACACACAGCAGGCTACCTGG2220               ACACCGAAGCTGAACAAGGCTACGTGTTTCACAAACTGCACCAGTACCACATAGAGGAAT2280               GTCAGGTAGCGTCTCTCCGCAAACAGCCGTTCCAAGTCTGAGGGCGTTACCCGCAGCGGC2340               AACCAGGGCAGCCTGGACGCCGGCCGGCAATGGAGCACGCTCCGGTTACAGGCACTGCAG2400               GGGTAAACGGTTAACATCACGTAAGAGAGTCGTGCGTCCACCTGTGGGAGCTCAGTTTCG2460               TAACGTAGAGCCCCGTCATTTTCCAGCTGGGGTGCGCCGACCTTGAAATGGGTCGCGCTC2520               CGCTCGTTACCCCAGGTGCCGTAGGCTCTCGGGGCCGTATCGGAGAAGTTGCCACGCACA2580               AGCCAGGCGGCCACGAGTACCCCGTGCTGGACGTAACATTCGGACACGGAACTGGAGACA2640               CGGTAGCCGGACACGTCCCCAAACCCGCGAGGGTACTGGGGCAGACGGACGGACTTGCTA2700               TTTGACAACGGACAGATACGAGACGACGAGGACGCAGACGACTCGTCGCTGGACCACGAC2760               AACCGGAGCGACTCCTTGGAGCGGCTCGAGAGTACACTTACTGCGATCAGACACCAGTGC2820               CAGAAGAAGGAACAGGTGGACGGGGACCACAGGATCATAGCCGCCGGCACCGCGGCCGGC2880               CGCAGGAAGCCGCCCGGCGCGTCGTCTGTGTGCGGGAGCCGAAACACCGTGCCTCTTTAT2940               ATCGTCCCGACGTGACGCGAGTATTACGTGTCAGGGGAAACCCCCGTCACGACGAACGTG3000               ATTTGTAAGTGACGCGGGGTGCTGACGGGGTTCGGCCCGAGAGGTGACGGAGCGCCTCAC3060               GTCAGTATGATGTCCGATCCGCGTCAGCCCCGACGTGGTTGTGGTCACCGAAACCCACGT3120               TTATATGGACGTTGAGAGCAGCGCCTGACCACATGATTCATCATACCATTTCTCGGAATC3180               GGGCCCATGCCGGGAAAGCACATTCCTTTTCAGTAAACAACAATGACATCATAACAAATC3240               ATTTTATTCGCGAGGTGGATAATAACCGCATATCAGGAGGAGGGATCGGGTGATGACGCA3300               GGCCCCGCAGAACAGTCCGAAATAAATTTTTAGTATTGCCCCATAGTCGCCTAGATACCA3360               GAGGTACGTTAAGTTCATCAAAACGCCCATCGGCGTCCCGGAATCGTATACCGGGCACAC3420               GAAGCGTTCATAACAATCCCGGGAGGCGAGTGTTAGGGTAGCAGAGTAGTTTCGGGGTCG3480               GTTTCCTTCCGGCGACGACAGTTCCGTGGGCAGCAGAATGTACAGCGCCTCGGTAGCTGT3540               CGCGGTGCCTTCCACGAGGATGGGCTGCCGGTGCCTTTCGTGATTTTCCCCGTCGTGTAG3600               CCAAGCCGAGGCCCGCAAAGTCTTAGGCGAGGGGAATTGTCCATAGAGTTTCACCGCACC3660               CTTCAGTACATGGTTCTGAATAACACAGCCGCACGTGAAGTAGGTAGGTTCTCTCGTCTC3720               CTCCGTGGCTGCCGCCACCACTCCCAGCCACCACAACAGGCAGATCGCCAGAGGGTTCCG3780               GAGGCTTCCCCGGCGTAGCATGGTTTTGGGTTAAAGCAAAAAGTCTGGTGAGTCGTTTCC3840               GAGCGACTCGAGATGCACTCCGCTTCAGTCTATATATCACCACTGGTCCGAAAACATCCA3900               GGGAAAATGTCGGTGCAGCCAACCTTTCACATACAGCCCCCAAAACACTTGAATCACTGC3960               CACCATCATCAGCGTATACTGCGCCGACTTAATCGTGAGCGCGTAGTACGCCATTAGACG4020               GCGATCTTCGAACAATAGTCGTTCGATGTCCTCTAACGAGCTCCACAGGGGAACCCAAGG4080               CACGAGGCACCGGGGTTCGCACTCTACATAATAAGTTTGGCATTGGTGGCAGGGGGAAAA4140               GTAGAACAACACGAGTTTTGTGCGTTGGGGAACACGATAGTCCCGGAGCCAGTAGCGTTT4200               TGCGACGAGGCTTTCGGAGACGTCCTCCACCGGCGTCGGCACTCGATCCGCGTAGCCCTC4260               CAGCGTCTGGTAGTACACCCGGGGTGTCGGCGTGGGCACGGACAGGTTCCCGCGCAGGGT4320               CCACAGAGCCTCCAGTCGACCGCCCGATCGGAGCACGCAGCGCGCCTCGGAATACTCTAC4380               TCGGTACTCCGAAACATCGGACAGAGGCGGTAACGGCTCCGTCTCCACCAAGGGCGGAGG4440               TTCATCGAAAAGAGTCAAGGATAATTCAGGCATACTACCCGCGACCGGGGCCCAGAGGGC4500               TAGAATAAGCATTACAAGGTTCATTCTGTCTTACAAGGGAAGGCTGTTACCCTGTCTAGA4560               CTCAAAAGCTGTAAGGCTGTCTTATAGCATGTAGTCTTGCACGTCACGGGGAACAGGGTG4620               GTGATCTAGTGACGTCGGGAGAACACGGTGTTTTAGGGTGCGGGGGACAAAGGACAGTAC4680               GACAGATTAGGTGATAGAAACGTTTTTTTTTATTTATGAAAAAGCCAGTGTGCCGTGCGG4740               CCTAGGGCCCCGGCGTAGTTTGGATACCAGATGGGGGCCGTCAGGGGTACTACCACGAGC4800               AGAAACATAATGACTTGGTCCATGTATAGCAGCATAGCGGTGCGCAGCAGGTCGCCGTCC4860               GTGTAGCAATTTGACGGTGAGCGATAAAGCACCGTTAATGTGTCGCGGATAAGCACGATC4920               TTGAGGCCGTAGATGAAGCTCACAGTCAGTGCTAAAATGATGCGTTGGTATGGTTCCCAG4980               GACTGCACGGCGATGAAGAGCCAGAGTATGGGAAGCATGA5020                                   (2) INFORMATION FOR SEQ ID NO:6:                                               (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 5924 base pairs                                                    (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6:                                        TCTAGACTCAAAAGCTGTAAGGCTGTCTTATAGCATGTAGTCTTGCACGTCACGGGGAAC60                 AGGGTGGTGATCTAGTGACGTCGGGAGAACACGGTGTTTTAGGGTGCGGGGGACAAAGGA120                CAGTACGACAGATTAGGTGATAGAAACGTTTTTTTTTATTTATGAAAAAGCCAGTGTGCC180                GTGCGGCCTAGGGCCCCGGCGTAGTTTGGATACCAGATGGGGGCCGTCAGGGGTACTACC240                ACGAGCAGAAACATAATGACTTGGTCCATGTATAGCAGCATAGCGGTGCGCAGCAGGTCG300                CCGTCCGTGTAGCAATTTGACGGTGAGCGATAAAGCACCGTTAATGTGTCGCGGATAAGC360                ACGATCTTGAGGCCGTAGATGAAGCTCACAGTCAGTGCTAAAATGATGCGTTGGTATGGT420                TCCCAGGACTGCACGGCGATGAAGAGCCAGAGTATGGGAAGCATGAAGCTTAGCAAACAG480                AGGATGGCTAACCGTCGTTGCATGTTCCAGGCCATGAGCCAGGCTAGGCCCGTACACCAG540                ACGCAGAGCATGGATGACAGGACATAGGCCTGGATTACCACGGTGCGATCGAAACACAGC600                CCGATGGTGGACACGGATATCGTAGTGAGGGTGGTATATACCATGACCAGCATCAGGGTC660                CCGGGTCGGCGCCGACGTTCCAGCCAGTACGCGTGGCAACGCAGAGCGCAGGGTAGCAGT720                GTGCTCCAGAAGGGCAATGTATCGCGCAGGTAGGGGGCCGTCACGCGCCACGGTATGAGC780                ATGAAAAGGATGGTAGTGGCTATGGTGGCGCTGGTCTGGAACACGACAGTGCCGTAGAGA840                CGTACCATCCAGAGAAAGTGTTGAACGCTCCGCAGGGTGTCTTCATCTTTGGTGATTACG900                GTGACTCGACGGATCGGCGGTGGTGACGGCGGCGACACGGGTGGGGGTTTCTCTTTCTTA960                TGGCCGAGTGGCTCGCCTTGGTGAAACTGGATCTGTACCATGACGGGTGCTCGACGAACA1020               GTCGTGGGGGCTTTAGGTACCCGGCAAGTTTTATAGAGAAAGGGGGACGATGGGTGGTGG1080               CTACGAGCCACCGCCACCTTCGCAATACGAGGATCTGAAGGCGGCAAAGACGGTCGTCCA1140               GGGCAGGCGCCAGAGGTTGGGACTGAGCACGATCAGCGTGATTTTAAACATGGTCACCAG1200               TCCTACGTAGATCAGCAGCGAGCCGCGTAACGTCTGAGCAGCCGGCAGTTCGTCGCGGAT1260               GTAACGCGTGCCGTAGAAAGTCACGGTCATCATAAGGAAGACGATGGCGCCGTAGCCGTA1320               GAGTAGAATACGCTGATGATGGAACACGGTCTGGTCGCCGATAACCCAGAGCGTGATGAA1380               AAAAACGCTGGTGAGTACCCGTGAGCATATGAGCTCCCAACGCTTAGCGCGAAAGCTGTC1440               CCCAACCATGACAGCGCCGGTGCAAGCTATCCACAGCGTGAGGACCAGTGTGTAGTCGAT1500               GAGGATGGCGGGCAGGTCGGAGCACCAGGTGTAGAAAACCGTGGTAACGGAGAGGAGGCC1560               TACGTAGCCCATGGTCAATACCACGTCGTCGGGGTGCCTTTCGCCCTGTATCAAGACCAA1620               ACACCAGAGAAGGGAGGGGGCAAAAACCAGCAGCAGAGGGGAAGATTCATGTTGACATAT1680               GTTGTGGGAATCGGGGATACCCAGCCAAATCATTCCGCAGAAAGCCGTACTGATGGCGAT1740               GTGAAAGACCACTAGGGCGTAGACCCGGACGAGGACAGCAAAACGGCGCAGCCACATAAG1800               GCCGTGGTGCAGCTGCAGGAGGGAAGCCCATTGCGGCGAATGTAGCGACGGTAGCGGCGG1860               GTCCATGAGGCGGGTGATGCGCCCGAGTGAACGGGTGAGCGTCTCGGTGGAGTCTTCTTA1920               TAAACCAGCGGAGCTCAGGCAGCCTTGCTCTGGAACGTCGCAGTGGTGGTGTTGAGGATG1980               ACGCTGAGCGTGCCGTTGTCAATCAGGTAATGATGATAGGTGCCGAGCTTGGCCAGGTAG2040               CTGAACATTTGGTCCCAGCGTGCCGACCACACCACGGGCGTGAGCATCAGGAGTGTGGTG2100               TGATAGATTAGTGTTTCGGTGGCGTAAAGTATCAGCGAGCTGCGGATGACGTGGCTCACG2160               GGCATTTTGGTGGCGATGTAGCGCACGTCTTGGAAAAGGACGGCCAGGATGCAGCCCACG2220               AACACGGTGTAGAGACACAGCAAAGTCTTATGTAACCAGGTGTAAGTAGAAGCCAGGACG2280               CTGACCATCACCGTCAAAAGTGTGGAGGTAAAAAGCGCGTCACGCCACACGGAGCTGAGA2340               CGGTGCTCCCAAGCCACGCCGTTGCAGGCCACGAACAACGTCCACGTTAGGATGAGGCTA2400               GAAATGCCGATGGGCGCTGTGGCGCACAGGTTGAGCCCGGCGGTGGTGAACGAGAGAAGC2460               GCCACATACAGCGCAAACACCAGGCCGTTGCTGGGGTGTCTGTGATCGGTGAGCTCCAGC2520               GCGCCCAGAACCAATACTGGTGTGCAGCTAAGCAATAGCGGCGAGGGATCGTCGCTGCAC2580               TTGTAGCCCAGCGAGGGGTAACCCAGCCAAACCAGCGCGCTAATGAGTACGCTGAAAGCG2640               GTTTCCAGCGTCAGCAATCCGTAGACACGCATGACAATCGCGGTCCGCCGTAGCCAACAC2700               ACGGCATCTTCGGAAACTGTGGACGCTGTTTCCGAATACCGGGAGGAGATCGTGCTTCCC2760               TCTTCCAAGGATCGGAAAGTAGCGTCCGTCGTTTCCGCGGACGCGGCTTCCCTGGTACGC2820               TCCGTTTCCGACGACGCGGTTTCCCGCTGCGTGGAAACTGTCTCCATGTCGGGACCGCAG2880               CGCCCGGCGGCGTATCCGCAAGGTCTCGAAGCTACAGCTTGTCAGAGGAAAAGTAGGTTT2940               GCAAAAAGGTGCGCAGGGTCATGATTCTCAGCACCATCAGCAGAGTGAAAACCAGACTGA3000               GAAACACCTTGACGGCCGCCAAAAGCGCGCGTTCCAGCGGCGTCTCGTAGCGTACAGCCA3060               GGGCCGCTTCGTGGAAATGCGAGACGGCTAGACAGGTAATGAGCACGCTGAAGGACAAGA3120               CGATCTTAAAGCACCAGGACCAACCACGCCTCAAGATGACCACCACGATTGCCGTGAAGG3180               TCAACGTGATCAAAGCATGGACGACCACGATCTGACGGCGGACGGTACGTTCGGGAGCCA3240               ACAACGCTACGCCGGTGCAGCTGAGAAAGGCCAGTAAGGTGAACAACGCGGCCGAGATGA3300               CCAACGTACCGTCCAGGCAGAGACATATCACGATCAACGGCGGCACGTGAAGCAGCGTGT3360               AAAAGAGCAGAACGCCGATATTGCTGGGATGCGATGTTTCGTAACAGTGAATGAAGATCA3420               CTGACGTGACGGGTATGACAAAGACGAGGCTGGGCGAGGACTCCGTGAGACACAGACGAG3480               AATGGTGAAACCACGTCGCGGGCGCCGCGTAGCAGAAGGCGCTCAACAACGCGGTCAAGC3540               CGGCCAGCTGCCAACCCACGGCGCCATAGGTGTGCAGCGCCACGCGGCAACAGTCGACCC3600               AAGCCAGACTGCGGGTCGCCAGCCGGGTCTCTTGGATCCCGGGGGGCACGTAGATGACCG3660               TGCCATCGGTGGGTACTTGAAACCCTTTTTCTCTTCTCATGGTGCGCTGCGTTCTCTGGA3720               AACGGCTGCTCTGTCCGAAAACCAGTTCCGAACGAAAATCTAGGGCGAGAGGGTGGACAA3780               CGGCGTCGACGACGAAGCATGGGACAGGTCGTTCGGCGTTAACGTCATCGCGTCGGACGA3840               CGGTAGTTCTAAGAGACGTAGATCGCTCAGCAGGTCCTGACAGTTGCGGATTCGCAAGAT3900               CAGAAAAAAAAGGGAAATGAACGTAATAAAGAGCTGTAGCGACGTATGCGCCACATCGCG3960               TGGCATAAGAACGTGACGGACGAAAAGGACCTGCTGCGAAAAGTGACCGGCGAAGATAAG4020               GCCCACCGTGCTGTAGAAGCCCAAAAGCAGCCGCAGGGGCCAAGTCCAGGGCCGCGTGAA4080               GACGATGAGAACGTTGACCAGAAAGACCACGACCCAGACGCCGTTGATGAGGGTAAATTG4140               ATCGGACAGGGTGCAGTTGTCGCGACAGATGAAGACTACTTCCGCGCAGAGCAAGGTGAT4200               GACCAACGTGAGCACAAACGACGTCAACACCTCGCGGGGCTCCTGGCAGGCACACGTGAC4260               ACCTAGCGCCGGGATGTGCGCCAGGAGGCCGGCGAGTAATAGCACCAGCTGTCGGAACGG4320               ACGACGGCAGCGCGGGTGCCGGTTTCGCTGAGCGAGAACCGGTCGCTCATAGCGGAAATA4380               CACGAAGAGCGCGGAGGCCACAGGCACCAGGAGGAGCACCTCGGGCGCCCAGACAACGTG4440               ACAAGGAAAGCCCGGACGCGACTTGAGAGTCGCTGTAGGGAAGACCAGAGAGAAGCTACC4500               CAAGACGGCCACCGCCGCGGAGATTTGGAAGAGGAGCAAGCCGGCGATTCGGACGACAAC4560               CTCGAAGCGATGCACCCAGCCCAGCACGGCCACCACGGCCGCTTCATCATAGTCGTCGTT4620               GTTGCCGCTGTCGAACAGCCGCCGAAACACGATCTGTCGCTGGGTCGCGGTGGGAAAGCG4680               CAGACCCATGACAGCCGGAGGCTATATGACCGCGCGTCTAAGACGCGAGATCCGTGGGGG4740               GACTTTTAGATGTTTGGGCGGCCCGCGGTTCTAACAGGCTTGATTGGTGGAGACGGCCGG4800               CGCGGCGGGTGGGGGAAACGACGAGTTTTTCCGTTACGCCATGGTTCGCGTGAGGTTTCT4860               CTGTACCTCCCGCAAAAGGTCACAGCCCGAAATGGAGGCCGCGTTGGTGGCCCCGGTGGC4920               GCGTGACGATAACCAGGTCATCCAAGCGATGAGTTTGTCTAATGAGTCCTCGGTGGTGAA4980               GAGGATGAGAATGAGCAGGTACAGGTACACCAGGTTCTCATAGAGACACAAGGTGAGCAG5040               GTCAGCCTCGGACCACGCGATCTCAAACAGGCGCGTGGTGTCAAAGACCGTGACGACCAG5100               CATGAAGCTGAGCGCCATGGCGTAATAGCCCAAAAAAAGTTTGTGCCCCAACGGTACGGG5160               CTGCAGGTAAAGTGCGATCAAGAACGCGATAACGCCGATCACAAACAGCGTGACGATGAC5220               CTGCCATCGACGGTGATTATGGCCGGCTAGACCCGTGACGCAGCTGCAGAGGCTAAAAAG5280               CACGCAAGCCAAGAGGCCCGAGAAGGTCACTAGCGTAGAGGAGGAGCAGGCGCTGGCCAC5340               GATCACCGAAAGCGTCGTGAGCACGCTATAAATGGTGAGCAGGCCAGGGCTCGGTGGCGA5400               CGTGAACGATCCTTCATCGCGTTTGCCGTGCAGCAGGGCCAAACAGATGGTGGGCACCAT5460               CAAACTTAAGGGCGGCATAAAGCCGGTGCAACAGAGAAAGACGGTGCCTTTAAGATGCGG5520               AAAAGCCAGCACCAGGCCCAGACAGAGCAAGAAGGTGCAGGTGCCCTGCACGGCCACGGT5580               GCTGTAGACCCGCATACAAAGTAAAAAGCGACGTACGTCGTTCGTCGACACGGAGGAAAT5640               CATAATGACTCCGCGCGAGGGTCGCGGGGGTGGGGGCGCCCAGGCCGTCCCGGTGGCCTC5700               TGAGTTCGGAGACATGACGGCGGTGGCGATCAAAAGGCGCGTATGAGAAACCGTTTATAG5760               AGTGTAATAGAATCACCGTCATTCCCACACGGCGTTCCCCCATAAAGTCACGTAACACTC5820               GAGTAAGCGTGAAAAAGCTTTATTGTTGAATAAAAAACACGAGTACAACACCGAGTTGCG5880               GTGTCCTGTCTGTCTACTGGGTGGGGAAGGTTCATCGTCTGTCT5924                               (2) INFORMATION FOR SEQ ID NO:7:                                               (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 1707 base pairs                                                    (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7:                                        AGCAGTGCTTCGCTGAGAAGTAGCGTGTGGACTGAACGGTGTTTTTGAATATATAGCGTT60                 TCTTGGTGACGTTGTTTCCCCTACGTAGTAGGCAACTACGTGCCAAAAGAGGCGTTACGG120                TACTTTCCGTACTGGGATTTCCAAACCGGGACTTTCCACACGGCGGTTTCAACACCGGGA180                CTTTTCACACGGTGATTTCGGCACCGGGACTTTCCGCACGGCGGTTTCGCCACCGCTGAC240                GTTCTCATCGCCGCCCACGTCAACGGTGGCGACACCGTACTTTCCCATGCGGTTTATAAA300                CGTCAAGAGTCACGTCAGTCGCCCACCCCCATTACACGGCGATATCCCGATAGGGCATGA360                GGGGACCCGGGTGTCGCGACATGTCGACGACAGGTGCGGATTAGTGGTCGTGTCGCGACA420                TGGACGTGCAGGGGGATGTCTGTCGCGATAGAGTTGATGTGACAGCCCGCTACACCTCTC480                TGTCGCGACATGCATACACAACGGGCCGGCTTGTCGGCGATTGTCGCGACATATCGTTAT540                CAGTTAGCGACCGGAGTTGTCTATCGCGACATATCGTCGACTATCGCGACAGAAAAAATA600                CCGTTCGTAGAGAATGCCGTGTTGAAGGAACGCGCTTTTATTGAGACGATAAAACAGCAT660                CAGGAGCCACAACGTCGAATCCCACGTCCAGTCGATTCGTATGTTATGCTGCACAGCAAT720                GCTAGAATAACAACCAGCAGGGTAATCCCGCAACATAAATACAAAGTCACAGCGAAGAAT780                CCGTGTCGTTCTATCAAGCGAAACGCGTTCCAAACGGCCCCGTCACAGACGCAGTTATTC840                ATAAGCGTTAACAACCGGTGGCTAGGATGAATATCCAAATCACAGGGCAGTAGCCGACGG900                ACTCGTTGACAGGTCAGCCTACCCTCAAGGTTCCTATCGTTCGGACGGGATTTGTGCGTT960                TTAGGCCTCTTTTTCGCCGCCTGCAAGCATTGGTGCGCAAAGTCCTCACCCAGCTGTTTC1020               CAGCTATCATCTGCATCTGTGCAGTCCCCTGTATCGTTGTAACAAACGGGTCTGTGCGAC1080               TTCGTTCTCGGAACACAAGCTTGTTGTCGCGGAGACAGAGAGAGAAGGGTTTTCGGGTCA1140               CGCGAAGACCGCTCACCGGGGGTCGGCAACGCACACATCAACAGAAAACCGAGACGAATC1200               AAGAGATCCATAGTGAAGGAGTGATATCGACGTGCTTACGAAACGGCGATTATATATGTT1260               CTCAACAATACCGCCCTACGTTGTATGATGTAACGTGTGACGTGAGTCTGATCCAACACT1320               GAACGCTTTCGTCGTGTTTTTCATGCAGCTTTTACAGACCATGACAAGCCTGACGAGAGC1380               GTTCATCGGGGCATGAAGTACGCATTACACAAACTCCATATATTTGTTACGATAGAATAC1440               GGAACGGAGGAGGCTTTCGCCACACCTATCCTGAAAGCGTTGCATTCTTTATGATAGGTG1500               TGACGATGTCTTTACCATTCCCACGGCTGCTTTGCGTGATGATGACATTCATCATGTATT1560               TCCATTCACACATACCTTTTGTGCATACGGTTTATATATGACCATCCACGCTTATAACGA1620               ACCTAACAGTTTATTAGCCCTTGACAGGATAGGTCAAAAGATTATATGTAGGTTTTCCGG1680               TAAACCGAATTGTGATATTTCTCTGCA1707                                                (2) INFORMATION FOR SEQ ID NO:8:                                               (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 1817 base pairs                                                    (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8:                                        TCTAGACTCAAAAGCTGTAAGGCTGTCTTATAGCATGTAGTCTTGCACGTCACGGGGAAC60                 AGGGTGGTGATCTAGTGACGTCGGGAGAACACGGTGTTTTAGGGTGCGGGGGACAAAGGA120                CAGTACGACAGATTAGGTGATAGAAACGTTTTTTTTTATTTATGAAAAAGCCAGTGTGCC180                GTGCGGCCTAGGGCCCCGGCGTAGTTTGGATACCAGATGGGGGCCGTCAGGGGTACTACC240                ACGAGCAGAAACATAATGACTTGGTCCATGTATAGCAGCATAGCGGTGCGCAGCAGGTCG300                CCGTCCGTGTAGCAATTTGACGGTGAGCGATAAAGCACCGTTAATGTGTCGCGGATAAGC360                ACGATCTTGAGGCCGTAGATGAAGCTCACAGTCAGTGCTAAAATGATGCGTTGGTATGGT420                TCCCAGGACTGCACGGCGATGAAGAGCCAGAGTATGGGAAGCATGAAGCTTAGCAAACAG480                AGGATGGCTAACCGTCGTTGCATGTTCCAGGCCATGAGCCAGGCTAGGCCCGTACACCAG540                ACGCAGAGCATGGATGACAGGACATAGGCCTGGATTACCACGGTGCGATCGAAACACAGC600                CCGATGGTGGACACGGATATCGTAGTGAGGGTGGTATATACCATGACCAGCATCAGGGTC660                CCGGGTCGGCGCCGACGTTCCAGCCAGTACGCGTGGCAACGCAGAGCGCAGGGTAGCAGT720                GTGCTCCAGAAGGGCAATGTATCGCGCAGGTAGGGGGCCGTCACGCGCCACGGTATGAGC780                ATGAAAAGGATGGTAGTGGCTATGGTGGCGCTGGTCTGGAACACGACAGTGCCGTAGAGA840                CGTACCATCCAGAGAAAGTGTTGAACGCTCCGCAGGGTGTCTTCATCTTTGGTGATTACG900                GTGACTCGACGGATCGGCGGTGGTGACGGCGGCGACACGGGTGGGGGTTTCTCTTTCTTA960                TGGCCGAGTGGCTCGCCTTGGTGAAACTGGATCTGTACCATGACGGGTGCTCGACGAACA1020               GTCGTGGGGGCTTTAGGTACCCGGCAAGTTTTATAGAGAAAGGGGGACGATGGGTGGTGG1080               CTACGAGCCACCGCCACCTTCGCAATACGAGGATCTGAAGGCGGCAAAGACGGTCGTCCA1140               GGGCAGGCGCCAGAGGTTGGGACTGAGCACGATCAGCGTGATTTTAAACATGGTCACCAG1200               TCCTACGTAGATCAGCAGCGAGCCGCGTAACGTCTGAGCAGCCGGCAGTTCGTCGCGGAT1260               GTAACGCGTGCCGTAGAAAGTCACGGTCATCATAAGGAAGACGATGGCGCCGTAGCCGTA1320               GAGTAGAATACGCTGATGATGGAACACGGTCTGGTCGCCGATAACCCAGAGCGTGATGAA1380               AAAAACGCTGGTGAGTACCCGTGAGCATATGAGCTCCCAACGCTTAGCGCGAAAGCTGTC1440               CCCAACCATGACAGCGCCGGTGCAAGCTATCCACAGCGTGAGGACCAGTGTGTAGTCGAT1500               GAGGATGGCGGGCAGGTCGGAGCACCAGGTGTAGAAAACCGTGGTAACGGAGAGGAGGCC1560               TACGTAGCCCATGGTCAATACCACGTCGTCGGGGTGCCTTTCGCCCTGTATCAAGACCAA1620               ACACCAGAGAAGGGAGGGGGCAAAAACCAGCAGCAGAGGGGAAGATTCATGTTGACATAT1680               GTTGTGGGAATCGGGGATACCCAGCCAAATCATTCCGCAGAAAGCCGTACTGATGGCGAT1740               GTGAAAGACCACTAGGGCGTAGACCCGGACGAGGACAGCAAAACGGCGCAGCCACATAAG1800               GCCGTGGTGCAGCTGCA1817                                                          (2) INFORMATION FOR SEQ ID NO:9:                                               (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 1702 base pairs                                                    (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9:                                        CCATGGTTCCGAAGCGTCCCCACATGCACCAGCAGTCGGCGTCAAAGTCGCTTGCGCTGT60                 CGGCCCAGTCGCCACCGCCGCGGCGGATTTCCGCGCGGGGGACGGGGTAGCCGAGTGCTG120                CGCCCTCGCCAATGTTGTGAAGTGGATGCGTGAGTTGATGTTGATTCTCTGTGGGAAAAT180                GAGCGCTGTCCTGTGGGTTGGTGTTGGGGTATGCGAGTAGTAGGGGTTGTGTTTGATCGT240                AGAGGTGTTGGCGGGCCTGTGCGCAAGCAGCGTAGTCTGCGGCGTCGAGCTCCATCTGTG300                TGCGGTGTTCTTCGTCGGCGTGTTTGTCCGAGGTTTGGACATGCGGTTGTGTGTTGCTGT360                GGTGTAAGGGTAACGTGTGTTGGGCGTCTGGGTGAAGCGGCGTGGTGTGGGTGCTGTTTG420                TGTCTGTGGCTGGCATGATTGTGCGGCATGTGTGTGTTGTAGTGGGTGGAGGTTAAATAG480                GTGAGGTGGGTTCCCTGGTCCGCGCCGCAAACTGTCCCCGTCCCCAACGTAACCTCCCCT540                ACGCGGCGCGAACAGCCCCGGCCCCAGCGCAACCCCCGTCCCCGGCCCCAACACCGTCCC600                GCACACCCCCCGTCTCCGCAACACCCCGGCATCGCCGGCGGCCAGAACGCTCGAAAACCC660                CCGACAAGCGCAGCGCCGAAACGACACAGGCAAGGACCGTGGAACGCACCGGCAGCGCGC720                CGAAACACCGTCCCGAAGCCCGGTGCCGACAACAAATACCGTGGGACGACACGCACCGGC780                AGTGCGCAGGCAGCGTCGGACACAACACGCTTACGGCCCTCAACACTCCCTCGAGGACCC840                ACCACGCGGCCCCGCACCGGCGGTGTTTTGGGTGTGTCGGGGCGCGGCCGGGTGGGTGTG900                TGCCGGGTGTGTCGCGGGCGTGTGTTGGGTGTGTCGGGGGTGTGTTGGCAGGGTGTGTCA960                GGGTGTGTCGCGGGCGTGTGCCGGGTGTGTCGTGCCGGGTGTGTCGCGGGCGTGTGGCGG1020               GTGTGCCGGCGGGGTGTGGTGGCGGGGTGTGTCGGCGGTGTGCGCGGCCTCGGGGTGTGC1080               GGCTTCGCAGGAACGAGTGTGTGGCCTCGCGGCCGTTATTTCCCCCGCGGTCCCCAGGGC1140               CGTCGTCCCTCGCCCCCGGGCGTTGCTTTTCGTGTGTCCCCAGGGACCCATGCTGCCGTC1200               CCCCGGGAACTTCCTCTTTTCCCCGGGGAATCACACAGACACAGACACGCGTCTTCTTTT1260               CGCCGTGCGCGCCGCACGTCGCTTTTATTCGCCGTCGCCGTCCTCCGCACCACACGCAAC1320               TAGTCGCCGTCCACACACGCAACTCCAAGTTTCACCCCCCCGCTAAAAACACCCCCCCGC1380               CCCTCGAGGACCCACCACGCGGCCCGGAATGGATGTCGGGCGTCCACCTAGATGGGTGCG1440               CGCCCGGGAGGCGGCTGTGCGCTCCAGTGGTACGCGCCTGCCGCGCGTCTTCCTTCGGGT1500               AGCTGCCTTTCCCAGTCCACGGCCTTCCAGACTGCGTGGCGCCAAGGCGGCGCCAGCACG1560               CGCCGTGCACGTCGCTGCCTATAAAAGCCAGCTGCGTGTCGCCCGCGGCACACGGGCGAC1620               GAAGGCGTCCGCGTGTCTAAACCGCGTGCTCGCTGACGCGGGTTTGCTTCCTATATAGTG1680               GACGTCGGAGGTGTCCGGCGCC1702                                                     (2) INFORMATION FOR SEQ ID NO:10:                                              (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 256 base pairs                                                     (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10:                                       CCATGCCGGGAAAGCACATTCCTTTTCAGTAAACAACAATGACATCATAACAAATCATTT60                 TATTCGCGAGGTGGATAATAACCGCATATCAGGAGGAGGGATCGGGTGATGACGCAGGCC120                CCGCAGAACAGTCCGAAATAAATTTTTAGTATTGCCCCATAGTCGCCTAGATACCAGAGG180                TACGTTAAGTTCATCAAAACGCCCATCGGCGTCCCGGAATCGTATACCGGGCACACGAAG240                CGTTCATAACAATCCC256                                                            (2) INFORMATION FOR SEQ ID NO:11:                                              (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 1328 base pairs                                                    (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11:                                       CCCGGCCCACCTCCGCTGCCGCCAAAGCAACGGCACGGTTCCACCGACGGAAAAGTTTCT60                 GCGCCCCGACAGTCGGAGCATCATAAAAGACAGACCCGACCGCCAAGGCCGCCACCGCCC120                AAATTCGGGGATAGAACCGCGGCCCATCTCTCGCAAAATATGCGGGACATGTACCTCGAT180                ATGTGTACATCTTCGGGCCACAGGCCACGGCCGCCAGCACCTCCGCGGCCGAAAAAATGT240                CAAACACACGCCCCTCACCACGTTCATCATTGAAAGTCTCTCCAGTCCATATGTTGTCAG300                GACGTGCTGTCGTTCTCCGCTTGCTGCGAAGCCCGTTCTTCCGAGTCGTGTCGCTGCGTC360                CAGCGTCGCGCCCAAGATGGGAATTTGGGTCTTTTCACGCGTAGCCTCCTCCACCACGGC420                TGCTGATCGCCGTCACTAAGGACCGACACGGAGGATGACGAGGAGCTTCTCCCCGACTCC480                GCGGTCCGCGACCGGCTACGTAGCGCGTGTCCCTGCCAGTCTCCGCAGTTACACCACACG540                TCGTGAGCAGCGTGCACCTGCTGCCGCCACTGGGCCTCGGCGTGCTCAGGCCACCCGCCG600                GAGCCCGGTCTGAGCTCCGACGCAGGATGCGCGTACTCAACGTGCGCCTTCCAGTCCATA660                CAGCAACACCATAGGTCGTGCGAGTCGTCGGCTACCCGCCGCCAGGCCAGTTCCCGCATG720                GGAAGGCTGGACACGCCGACCGAGAGGTCACCGAGCCCGGACGCCATCTCTTCTTCCTCT780                CCGTCGCTGTCATTAAGCAGCCAGGTCACCTCCTCCGCTCCGCGTCCGCCGGTCTCGACG840                GACCGCGCCGCCGTCGGCAACACGGAAAACAGCACGCCAGCCCGAGCCGCTAAGGCCGCA900                TGCCCCTGCCGCCCAACTGAACACGCATACCCCGCTCAACTGCGTTTTGCCACCCCTGTC960                AGTGCTCTCGCTCGAGCACCACCCCGCATCTCCCAACCTTTTTCCAATAAACGAAACCGA1020               CATGACACACGTAATGGGTACTCGTGGCTAGATTTATTGAAATAAACCGCGATCCCGGGC1080               GTCTCAGCACACGAAAAACCGCATCCACATCATAGACAAGTTACAGTCCACAGTCACATA1140               CACGATAAACAATACCAACAGGGTAATGTTTATGGAGTAAAACACTATTGTCCAGGCCAC1200               ATGCGTGTATGACTTCCGCACCATCCCGTACTGCATGTTCCACATGTACGCGCTAGACGT1260               GTAATCCACTCGCAGTTCGGGGACGCAACGCAGCCAGATCACATCCCCTTGCAGTACCAG1320               ACGCAGGG1328                                                                   (2) INFORMATION FOR SEQ ID NO:12:                                              (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 1528 base pairs                                                    (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12:                                       CGGCCTGGGTGTTAGAGTCCGTACCTTGCAGCCCAGGTAGGTTTCAGGTACCAGCTGGTT60                 CGTACCTGTTAAATAAATCGCAGACGGGCGCTCACCCCTACGGTCAGGAGCACAAGAACA120                ACCAGAGAGAACAGATATACGAGCAGGGTTCTGAACAGCAGACCCCAATTGTCGTCTCTC180                ATGCTTCGCTGAAGGTACCAGTTGATGGTCTGAGAGCTATAGTCCATCCTCACCTGAGGA240                ACACACGCGGCATATTTCTTGGGGTCTCCCCACCTCGTAGACAACGTGATGTCCACCATA300                TCCACGGTGTGCGTCACCGGGTGCCCACCGATGTTCCACTCGAAATAGGCTCCGCGCTCA360                TCATGGTGGTACTGCTCACCGGACACCTGCAGTCTGTCCATGTAAGATTGAGAGACGATA420                CCCACGTTCACAAAGTGTTTCTCGGTGAAGTTGCCCGACATCCTCCCCTTGAAGTACAGC480                ATGCCCATATGGAACCAGCATTGGTTCTCCTCCACTCGAAAGTGGGCCGATCTGATCTCC540                GATACCACCACATCCAGGGGCCGGGGCACCGAGTCCGCGAGTCTCAGGAACAAGACGGCC600                AGGATCGCGAGCACCAACACCGGCTTCATGGCTCCGAAGGTCCGCTGCTCGGCTCCGCTC660                ACCGCTCCGGTCTGGCTGCAGCAGTGCTTCGCTGAGAAGTAGCGTGTGGACTGAACGGTG720                TTTTTGAATATATAGCGTTTCTTGGTGACGTTGTTTCCCCTACGTAGTAGGCAACTACGT780                GCCAAAAGAGGCGTTACGGTACTTTCCGTACTGGGATTTCCAAACCGGGACTTTCCACAC840                GGCGGTTTCAACACCGGGACTTTTCACACGGTGATTTCGGCACCGGGACTTTCCGCACGG900                CGGTTTCGCCACCGCTGACGTTCTCATCGCCGCCCACGTCAACGGTGGCGACACCGTACT960                TTCCCATGCGGTTTATAAACGTCAAGAGTCACGTCAGTCGCCCACCCCCATTACACGGCG1020               ATATCCCGATAGGGCATGAGGGGACCCGGGTGTCGCGACATGTCGACGACAGGTGCGGAT1080               TAGTGGTCGTGTCGCGACATGGACGTGCAGGGGGATGTCTGTCGCGATAGAGTTGATGTG1140               ACAGCCCGCTACACCTCTCTGTCGCGACATGCATACACAACGGGCCGGCTTGTCGGCGAT1200               TGTCGCGACATATCGTTATCAGTTAGCGACCGGAGTTGTCTATCGCGACATATCGTCGAC1260               TATCGCGACAGAAAAAATACCGTTCGTAGAGAATGCCGTGTTGAAGGAACGCGCTTTTAT1320               TGAGACGATAAAACAGCATCAGGAGCCACAACGTCGAATCCCACGTCCAGTCGATTCGTA1380               TGTTATGCTGCACAGCAATGCTAGAATAACAACCAGCAGGGTAATCCCGCAACATAAATA1440               CAAAGTCACAGCGAAGAATCCGTGTCGTTCTATCAAGCGAAACGCGTTCCAAACGGCCCC1500               GTCACAGACGCAGTTATTCATAAGCGTT1528                                               (2) INFORMATION FOR SEQ ID NO:13:                                              (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 1151 base pairs                                                    (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13:                                       CCATGCCGGGAAAGCACATTCCTTTTCAGTAAACAACAATGACATCATAACAAATCATTT60                 TATTCGCGAGGTGGATAATAACCGCATATCAGGAGGAGGGATCGGGTGATGACGCAGGCC120                CCGCAGAACAGTCCGAAATAAATTTTTAGTATTGCCCCATAGTCGCCTAGATACCAGAGG180                TACGTTAAGTTCATCAAAACGCCCATCGGCGTCCCGGAATCGTATACCGGGCACACGAAG240                CGTTCATAACAATCCCGGGAGGCGAGTGTTAGGGTAGCAGAGTAGTTTCGGGGTCGGTTT300                CCTTCCGGCGACGACAGTTCCGTGGGCAGCAGAATGTACAGCGCCTCGGTAGCTGTCGCG360                GTGCCTTCCACGAGGATGGGCTGCCGGTGCCTTTCGTGATTTTCCCCGTCGTGTAGCCAA420                GCCGAGGCCCGCAAAGTCTTAGGCGAGGGGAATTGTCCATAGAGTTTCACCGCACCCTTC480                AGTACATGGTTCTGAATAACACAGCCGCACGTGAAGTAGGTAGGTTCTCTCGTCTCCTCC540                GTGGCTGCCGCCACCACTCCCAGCCACCACAACAGGCAGATCGCCAGAGGGTTCCGGAGG600                CTTCCCCGGCGTAGCATGGTTTTGGGTTAAAGCAAAAAGTCTGGTGAGTCGTTTCCGAGC660                GACTCGAGATGCACTCCGCTTCAGTCTATATATCACCACTGGTCCGAAAACATCCAGGGA720                AAATGTCGGTGCAGCCAACCTTTCACATACAGCCCCCAAAACACTTGAATCACTGCCACC780                ATCATCAGCGTATACTGCGCCGACTTAATCGTGAGCGCGTAGTACGCCATTAGACGGCGA840                TCTTCGAACAATAGTCGTTCGATGTCCTCTAACGAGCTCCACAGGGGAACCCAAGGCACG900                AGGCACCGGGGTTCGCACTCTACATAATAAGTTTGGCATTGGTGGCAGGGGGAAAAGTAG960                AACAACACGAGTTTTGTGCGTTGGGGAACACGATAGTCCCGGAGCCAGTAGCGTTTTGCG1020               ACGAGGCTTTCGGAGACGTCCTCCACCGGCGTCGGCACTCGATCCGCGTAGCCCTCCAGC1080               GTCTGGTAGTACACCCGGGGTGTCGGCGTGGGCACGGACAGGTTCCCGCGCAGGGTCCAC1140               AGAGCCTCCAG1151                                                                (2) INFORMATION FOR SEQ ID NO:14:                                              (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 1809 base pairs                                                    (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14:                                       GCATTCTTTATGATAGGTGTGACGATGTCTTTACCATTCCCACGGCTGCTTTGCGTGATG60                 ATGACATTCATCATGTATTTCCATTCACACATACCTTTTGTGCATACGGTTTATATATGA120                CCATCCACGCTTATAACGAACCTAACAGTTTATTAGCCCTTGACAGGATAGGTCAAAAGA180                TTATATGTAGGTTTTCCGGTAAACCGAATTGTGATATTTCTCTGCAGGAAATAGAACAGC240                CTGGTACCTATAAAACGGACAATGCAGTACTGTAGCAGCGTAACCAAGTAGGTCCACATG300                AACACGTACAAAATTATGGTAAGCCATCGTTTTTCATACCACAGCCTGTAGCTGTCGTAC360                ATGAATGAGGACGGTCGAGGAACCCAGGGTAGTTGTAATTGGGGGCGACATTCGTACTGT420                CCAGAAGACAATTGCACGGGTTTCAGTGAGATGAGTACTTTAGCGATGTCGGCGGGGGCG480                CTACGTTTCACCGTGACGGTGAGAACTTGACCGTCGTTTTGTATTTCATGAGGCACGTTA540                TACAAGCCACTGGTATCATGAAGGATGACCTCTGATGCGATGTGAGGATTAAATTGTCCC600                TCAAACCGCCAAACGCTGGTCATGTTTCCACCGTCAATTACGCAGCTGACGGTGTGAGAT660                ACCACGATGTTGGACTTAGGTTTGGGGGCTAATTGCCTTTTTACAAATTCCCTTCTGTAT720                TGCAGGTCCTGCTGCCACTGCTTTTCCGTGCGGAAAGTCGCCATGTCTTCCACACGTGTG780                GCGACGATAGACGCCACCAAGGTAGCTACCAGAAGCAGCTGGATCCGCATGGCATTACCG840                TATGTCAATTAGAAAGTTGAGCGGACACGGTTATCGTTCCTGGCGGATATAAGTATATAA900                ACGCGAGTTAGCCTTTCCCGTCCGTTTTGTACACCCGTTCCCCACACAAATGACGAATAC960                GACCTTTTTTTTTATAAAAATAAACCACGTGTATTATATAAAAACATTTACATAGAAAAG1020               AGACACACGGATCAACATAAGGACTTTTCACACTTTTGGGGTACACAGGCGTGCCACCGC1080               AGATAGTAAGCGCTGGATACACGGTACACAGTCCTGGCCAGCACGTATCCCAACAGCAGC1140               ACCATCGCCATACAGATGGCGATCACGACCCCGAGCTCTAAGTGTCTGTATTCATAGTGT1200               AGTCGCCGCAGGTTATCCACTGAATTCCCGTAACTGAAATAACGTATATGGTACCGAGGC1260               TGGCACCACATGGGTTTGCATTTGGTGCACGGCACCAAATGCAGAGTGAGATGGTCCAAG1320               TCCGTGGGCACCCACTGGCGCAAACGGAATACGGCTTCGGTGGTCTCCACGAGGCACTCC1380               GGGGCGTGCAGACGGCCCCACTTTCGTCCGCGACGGCCCGACCAGCCGACCCGAGCCACT1440               ATCCCTTTCTCGGGATAGAACGTACCCTGTACACGCCACACAGCGTCCAACACGCCGTCC1500               TTGACGACGCAGCTGGCCTGATAGCTGGACACGTTGTTAAGCGGCGGAAAGCGAAACTGA1560               CGTGCCGGCGGAGCCACATAGTTCGGTTCACCGTGTTGTCGCGGTTCGTCCTCCCTATAG1620               TAATAGTAGTCGTCGTCCTCATAGGGGTTGCCGGCGTGAGCCAGCGTTACCCAACAGCAG1680               CCCAGGCCGACGAGGAGGCGCAGCCACCGCCTCATGGCGGCTTCGCCAGTCAATCGTCTT1740               TAGCCTCTTCTTCCCGTGAGGTCCTTCCGGTGGCGCGGTGCCGACCTCGGACCCAGGGAC1800               GTATCCACC1809                                                                  (2) INFORMATION FOR SEQ ID NO:15:                                              (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 1765 base pairs                                                    (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15:                                       TCGCCGCCAGCGGCGAGCGGCACGGAGACGGAGGCCGCCGGCGGGGACGCGCCGTGCGCG60                 ATAGCGGGAGCCGTGGGGTCCGCTGTACCTGTGCCTCCGCAGCCGTACGGCGCCGCCGGC120                GGGGGCGCGATTTGCGTGCCTAACGCGGACGCGCACGCGGTGGTCGGGGCGGACGCGGCA180                GCAGCAGCGGCGCCGACGGTGATGGTGGGTTCGACAGCGATGGCGGGTCCGGCGGCGTCG240                GGGACCGTGCCGCGCGCCATGCTGGTGGTGCTGCTGGACGAGCTGGGCGCCGTGTTCGGG300                TACTGCCCGCTGGACGGGCACGTGTACCCGCTGGCGGCGGAGCTGTCGCACTTTCTGCGC360                GCGGGCGTGCTGGGCGCGCTGGCGCTGGGACGCGAGTCGGCGCCCGCCGCCGAGGCCGCG420                CGGCGGCTGCTGCCCGAGCTGGACCGCGAGCAGTGGGAGCGGCCGCGCTGGGACGCGCTG480                CACCTGCACCCGCGCGCCGCGCTGTGGGCGCGCGAGCCGCACGGGCAGTGGGAGTTCATG540                TTTCGCGAACAACGCGGTGACCCCATAAATGATCCCCTCGCATTTCGTCTTTCGGACGCT600                CGAACTCTCGGTCTCGACCTCACCACCGTCATGACAGAGCGTCAAAGTCAATTGCCCGAA660                AAGTATATCGGTTTCTATCAGATTAGGAAACCTCCTTGGCTCATGGAACAACCTCCACCC720                CCATCTCGCCAAACCAAACCGGACGCTGCAACGATGCCCCCACCGCTCAGTGCTCAGGCA780                AGCGTCAGCTACGCGCTCCGATACGATGACGAGTCCTGGCGCCCGCTCAGCACAGTTGAC840                GACCACAAAGCCTGGTTGGATCTCGACGAATCACATTGGGTCCTCGGGGACAGCCGACCC900                GACGATATAAAACAACGCAGACTGCTGAAGGCCACTCAACGACGAGGCGCCGAAATCGAC960                AGACCCATGCCTGTCGTGCCTGAAGAATGTTACGACCAACGCTTCACTACCGAAGGCCAC1020               CAGGTCATCCCGTTGTGCGCGTCCGAACCCGAGGATGACGACGAAGATCCTACCTACGAC1080               GAATTGCCGTCGCGCCCACCCCAGAAACATAAGCCGCCAGACAAACCTCCGCGCTTATGC1140               AAAACGGGCCCCGGCCCACCTCCGCTGCCGCCAAAGCAACGGCACGGTTCCACCGACGGA1200               AAAGTTTCTGCGCCCCGACAGTCGGAGCATCATAAAAGACAGACCCGACCGCCAAGGCCG1260               CCACCGCCCAAATTCGGGGATAGAACCGCGGCCCATCTCTCGCAAAATATGCGGGACATG1320               TACCTCGATATGTGTACATCTTCGGGCCACAGGCCACGGCCGCCAGCACCTCCGCGGCCG1380               AAAAAATGTCAAACACACGCCCCTCACCACGTTCATCATTGAAAGTCTCTCCAGTCCATA1440               TGTTGTCAGGACGTGCTGTCGTTCTCCGCTTGCTGCGAAGCCCGTTCTTCCGAGTCGTGT1500               CGCTGCGTCCAGCGTCGCGCCCAAGATGGGAATTTGGGTCTTTTCACGCGTAGCCTCCTC1560               CACCACGGCTGCTGATCGCCGTCACTAAGGACCGACACGGAGGATGACGAGGAGCTTCTC1620               CCCGACTCCGCGGTCCGCGACCGGCTACGTAGCGCGTGTCCCTGCCAGTCTCCGCAGTTA1680               CACCACACGTCGTGAGCAGCGTGCACCTGCTGCCGCCACTGGGCCTCGGCGTGCTCAGGC1740               CACCCGCCGGAGCCCGGTCTGAGCT1765                                                  (2) INFORMATION FOR SEQ ID NO:16:                                              (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 1611 base pairs                                                    (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16:                                       GCCCCTGCCGCCCAACTGAACACGCATACCCCGCTCAACTGCGTTTTGCCACCCCTGTCA60                 GTGCTCTCGCTCGAGCACCACCCCGCATCTCCCAACCTTTTTCCAATAAACGAAACCGAC120                ATGACACACGTAATGGGTACTCGTGGCTAGATTTATTGAAATAAACCGCGATCCCGGGCG180                TCTCAGCACACGAAAAACCGCATCCACATCATAGACAAGTTACAGTCCACAGTCACATAC240                ACGATAAACAATACCAACAGGGTAATGTTTATGGAGTAAAACACTATTGTCCAGGCCACA300                TGCGTGTATGACTTCCGCACCATCCCGTACTGCATGTTCCACATGTACGCGCTAGACGTG360                TAATCCACTCGCAGTTCGGGGACGCAACGCAGCCAGATCACATCCCCTTGCAGTACCAGA420                CGCAGGGCTAGCGTCTCGAAGATCGGCATCACATCTAAGTTCCGCACGTTCCACTTTAAC480                GACTCCCCGGGAACGAACTCCACGTCGTCGGCGTGTACGTACAGGTTCTCTCCCACGCCG540                CCATAATCGGCCTTCGGATCGAAGACGAACCGACTCATGTTGCCCACGATGCTCCCCCGA600                GCAAACAACTTGCCGTTGTCAATGTAGCACCGGTTGTCCTCGATTTGAAACCAGGGATGC660                TTGGCCGTGGACTTCCAGGGCCGGAGCGCGTCTTCCCCGGCTTTAGTGATTCCATCGGGC720                AGGCGGATCAAGGGACCCATGGAGGTCCAAAGACCCACCCAGGCTTTCCAGAGATTGTTC780                ATGGTGAAACAGCGTGTGGACTGTACGCTCTTTCCCAATTTATATCCCAGAGTAGTGACG840                TGAGCCCAGCCACCTCCCAGATTCCTGACGTTTTGGTTGTCTTTCCTGCCAATTCCTCCC900                GTAAACTTATGATTATCCTAGCCCATTCCCGATAAAAATACACGGAGACAGTAGATAGAG960                TTACGAATAAACCGGTTTATTTATTCAAGTGTCTCAGGAGATTATTGAACGAGCGTGGAT1020               ACCACGCCGTCGTCAGTTCATGGTGGCATTGAGCAGCCATAGCACCAGAGTCCCGGCGCC1080               CGGTATCAGACACGCTGACCTACCGGGCGCCTTCGAGTCCGTACCCCGCGGCCTGGGTGT1140               TAGAGTCCGTACCTTGCAGCCCAGGTAGGTTTCAGGTACCAGCTGGTTCGTACCTGTTAA1200               ATAAATCGCAGACGGGCGCTCACCCCTACGGTCAGGAGCACAAGAACAACCAGAGAGAAC1260               AGATATACGAGCAGGGTTCTGAACAGCAGACCCCAATTGTCGTCTCTCATGCTTCGCTGA1320               AGGTACCAGTTGATGGTCTGAGAGCTATAGTCCATCCTCACCTGAGGAACACACGCGGCA1380               TATTTCTTGGGGTCTCCCCACCTCGTAGACAACGTGATGTCCACCATATCCACGGTGTGC1440               GTCACCGGGTGCCCACCGATGTTCCACTCGAAATAGGCTCCGCGCTCATCATGGTGGTAC1500               TGCTCACCGGACACCTGCAGTCTGTCCATGTAAGATTGAGAGACGATACCCACGTTCACA1560               AAGTGTTTCTCGGTGAAGTTGCCCGACATCCTCCCCTTGAAGTACAGCATG1611                        (2) INFORMATION FOR SEQ ID NO:17:                                              (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 1174 base pairs                                                    (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17:                                       GCGCCGAAATCGACAGACCCATGCCTGTCGTGCCTGAAGAATGTTACGACCAACGCTTCA60                 CTACCGAAGGCCACCAGGTCATCCCGTTGTGCGCGTCCGAACCCGAGGATGACGACGAAG120                ATCCTACCTACGACGAATTGCCGTCGCGCCCACCCCAGAAACATAAGCCGCCAGACAAAC180                CTCCGCGCTTATGCAAAACGGGCCCCGGCCCACCTCCGCTGCCGCCAAAGCAACGGCACG240                GTTCCACCGACGGAAAAGTTTCTGCGCCCCGACAGTCGGAGCATCATAAAAGACAGACCC300                GACCGCCAAGGCCGCCACCGCCCAAATTCGGGGATAGAACCGCGGCCCATCTCTCGCAAA360                ATATGCGGGACATGTACCTCGATATGTGTACATCTTCGGGCCACAGGCCACGGCCGCCAG420                CACCTCCGCGGCCGAAAAAATGTCAAACACACGCCCCTCACCACGTTCATCATTGAAAGT480                CTCTCCAGTCCATATGTTGTCAGGACGTGCTGTCGTTCTCCGCTTGCTGCGAAGCCCGTT540                CTTCCGAGTCGTGTCGCTGCGTCCAGCGTCGCGCCCAAGATGGGAATTTGGGTCTTTTCA600                CGCGTAGCCTCCTCCACCACGGCTGCTGATCGCCGTCACTAAGGACCGACACGGAGGATG660                ACGAGGAGCTTCTCCCCGACTCCGCGGTCCGCGACCGGCTACGTAGCGCGTGTCCCTGCC720                AGTCTCCGCAGTTACACCACACGTCGTGAGCAGCGTGCACCTGCTGCCGCCACTGGGCCT780                CGGCGTGCTCAGGCCACCCGCCGGAGCCCGGTCTGAGCTCCGACGCAGGATGCGCGTACT840                CAACGTGCGCCTTCCAGTCCATACAGCAACACCATAGGTCGTGCGAGTCGTCGGCTACCC900                GCCGCCAGGCCAGTTCCCGCATGGGAAGGCTGGACACGCCGACCGAGAGGTCACCGAGCC960                CGGACGCCATCTCTTCTTCCTCTCCGTCGCTGTCATTAAGCAGCCAGGTCACCTCCTCCG1020               CTCCGCGTCCGCCGGTCTCGACGGACCGCGCCGCCGTCGGCAACACGGAAAACAGCACGC1080               CAGCCCGAGCCGCTAAGGCCGCATGCCCCTGCCGCCCAACTGAACACGCATACCCCGCTC1140               AACTGCGTTTTGCCACCCCTGTCAGTGCTCTCGC1174                                         (2) INFORMATION FOR SEQ ID NO:18:                                              (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 66 base pairs                                                      (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18:                                       CCATGCCGGGAAAGCACATTCCTTTTCAGTAAACAACAATGACATCATAACAAATCATTT60                 TATTCG66                                                                       (2) INFORMATION FOR SEQ ID NO:19:                                              (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 645 base pairs                                                     (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19:                                       CCACTGGTCCGAAAACATCCAGGGAAAATGTCGGTGCAGCCAACCTTTCACATACAGCCC60                 CCAAAACACTTGAATCACTGCCACCATCATCAGCGTATACTGCGCCGACTTAATCGTGAG120                CGCGTAGTACGCCATTAGACGGCGATCTTCGAACAATAGTCGTTCGATGTCCTCTAACGA180                GCTCCACAGGGGAACCCAAGGCACGAGGCACCGGGGTTCGCACTCTACATAATAAGTTTG240                GCATTGGTGGCAGGGGGAAAAGTAGAACAACACGAGTTTTGTGCGTTGGGGAACACGATA300                GTCCCGGAGCCAGTAGCGTTTTGCGACGAGGCTTTCGGAGACGTCCTCCACCGGCGTCGG360                CACTCGATCCGCGTAGCCCTCCAGCGTCTGGTAGTACACCCGGGGTGTCGGCGTGGGCAC420                GGACAGGTTCCCGCGCAGGGTCCACAGAGCCTCCAGTCGACCGCCCGATCGGAGCACGCA480                GCGCGCCTCGGAATACTCTACTCGGTACTCCGAAACATCGGACAGAGGCGGTAACGGCTC540                CGTCTCCACCAAGGGCGGAGGTTCATCGAAAAGAGTCAAGGATAATTCAGGCATACTACC600                CGCGACCGGGGCCCAGAGGGCTAGAATAAGCATTACAAGGTTCAT645                               (2) INFORMATION FOR SEQ ID NO:20:                                              (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 709 base pairs                                                     (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                           (ii) MOLECULE TYPE: DNA (genomic)                                              (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20:                                       CTCGAGATGCACTCCGCTTCAGTCTATATATCACCACTGGTCCGAAAACATCCAGGGAAA60                 ATGTCGGTGCAGCCAACCTTTCACATACAGCCCCCAAAACACTTGAATCACTGCCACCAT120                CATCAGCGTATACTGCGCCGACTTAATCGTGAGCGCGTAGTACGCCATTAGACGGCGATC180                TTCGAACAATAGTCGTTCGATGTCCTCTAACGAGCTCCACAGGGGAACCCAAGGCACGAG240                GCACCGGGGTTCGCACTCTACATAATAAGTTTGGCATTGGTGGCAGGGGGAAAAGTAGAA300                CAACACGAGTTTTGTGCGTTGGGGAACACGATAGTCCCGGAGCCAGTAGCGTTTTGCGAC360                GAGGCTTTCGGAGACGTCCTCCACCGGCGTCGGCACTCGATCCGCGTAGCCCTCCAGCGT420                CTGGTAGTACACCCGGGGTGTCGGCGTGGGCACGGACAGGTTCCCGCGCAGGGTCCACAG480                AGCCTCCAGTCGACCGCCCGATCGGAGCACGCAGCGCGCCTCGGAATACTCTACTCGGTA540                CTCCGAAACATCGGACAGAGGCGGTAACGGCTCCGTCTCCACCAAGGGCGGAGGTTCATC600                GAAAAGAGTCAAGGATAATTCAGGCATACTACCCGCGACCGGGGCCCAGAGGGCTAGAAT660                AAGCATTACAAGGTTCATTCTGTCTTACAAGGGAAGGCTGTTACCCTGT709                           __________________________________________________________________________ 

What is claimed is:
 1. A pharmaceutical composition comprising a recombinant human cytomegalovirus (HCMV) which comprises a genome from which a gene sequence comprising open reading frames IRS-1 to US11 has been deleted, and a pharmaceutically acceptable vehicle.
 2. A pharmaceutical composition comprising a recombinant HCMV which comprises a genome from which a gene sequence comprising open reading frames IRS-1 to US9 and US11 has been deleted, and a pharmaceutically acceptable vehicle.
 3. A pharmaceutical composition comprising a recombinant HCMV which comprises a genome from which a gene sequence comprising open reading frames US2 to US11 has been deleted, and a pharmaceutically acceptable vehicle.
 4. A pharmaceutical composition comprising a recombinant HCMV which comprises a genome from which a gene sequence comprising subregion A and a gene sequence comprising subregion B have been deleted, wherein said subregion A comprises open reading frames US2 to US5 and said subregion B comprises open reading frame US11, and a pharmaceutically acceptable vehicle.
 5. The pharmaceutical composition of claim 4 wherein said subregion B further comprises open reading frame US10.
 6. A vaccine composition for use in the prevention of cytomegalovirus infections which comprises an effective amount of a recombinant HCMV comprising a genome from which a gene sequence comprising open reading frames IRS-1 to US11 has been deleted, in a pharmaceutically acceptable vehicle.
 7. The vaccine composition of claim 6, further comprising an adjuvant.
 8. A vaccine composition for use in the prevention of cytomegalovirus infections which comprises an effective amount of a recombinant HCMV comprising a genome from which a gene sequence comprising open reading frames IRS-1 to US9 and US11 has been deleted, in a pharmaceutically acceptable vehicle.
 9. A vaccine composition for use in the prevention of cytomegalovirus infections which comprises an effective amount of a recombinant HCMV comprising a genome from which a gene sequence comprising open reading frames US2 to US11 has been deleted, in a pharmaceutically acceptable vehicle.
 10. A vaccine composition for use in the prevention of cytomegalovirus infections which comprises an effective amount of a recombinant HCMV comprising a genome from which a gene sequence comprising subregion A and a gene sequence comprising subregion B have been deleted, wherein said subregion A comprises open reading frames US2 to US5 and said subregion B comprises open reading frame US11, in a pharmaceutically acceptable vehicle.
 11. The vaccine composition of claim 10, wherein said subregion B further comprises open reading frame US10.
 12. A method of immunizing an individual against cytomegalovirus comprising administering to the individual an immunogenic amount of a recombinant HCMV comprising a genome from which a gene sequence comprising open reading frames IRS-1 to US11 has been deleted.
 13. A method of immunizing an individual against cytomegalovirus comprising administering to the individual an immunogenic amount of a recombinant HCMV comprising a genome from which a gene sequence comprising open reading frames IRS-1 to US9 and US11 has been deleted.
 14. A method of immunizing an individual against cytomegalovirus comprising administering to the individual an immunogenic amount of a recombinant HCMV comprising a genome from which a gene sequence comprising open reading frames US2 to US11 has been deleted.
 15. A method of immunizing an individual against cytomegalovirus comprising administering to the individual an immunogenic amount of a recombinant HCMV comprising a genome from which a gene sequence comprising subregion A and a gene sequence comprising subregion B have been deleted, wherein said subregion A comprises open reading frames US2 to US5 and said subregion B comprises open reading frame US11.
 16. The method of claim 15, wherein said subregion B further comprises open reading frame US10.
 17. A method of preventing or reducing susceptibility to acute cytomegalovirus in an individual comprising administering to the individual an immunogenic amount of a recombinant HCMV comprising a genome from which a gene sequence comprising open reading frames IRS-1 to US11 has been deleted.
 18. A method of preventing or reducing susceptibility to acute cytomegalovirus in an individual comprising administering to the individual an immunogenic amount of a recombinant HCMV comprising a genome from which a gene sequence comprising open reading frames IRS-1 to US9 and US11 has been deleted.
 19. A method of preventing or reducing susceptibility to acute cytomegalovirus in an individual comprising administering to the individual an immunogenic amount of a recombinant HCMV comprising a genome from which a gene sequence comprising open reading frames US2 to US11 has been deleted.
 20. A method of preventing or reducing susceptibility to acute cytomegalovirus in an individual comprising administering to the individual an immunogenic amount of a recombinant HCMV comprising a genome from which a gene sequence comprising subregion A and a gene sequence comprising subregion B have been deleted, wherein said subregion A comprises open reading frames US2 to US5 and said subregion B comprises open reading frame US11.
 21. The method of claim 20, wherein said subregion B further comprises open reading frame US10. 